mechanical-stimulation-induced-calcium-wave-propagation-cell

Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells

Intercellular communication is essential for the coordination of physiological processes between cells in a variety of organs and tissues, including the ...

KU Leuven

Thrombin, a serine protease, breaks down the barrier integrity of corneal endothelial cells by phosphorylation of the regulatory light chain of myosin II (myosin light chain; MLC), which induces contractility of the actin cytoskeleton. This study was undertaken to investigate the effect of thrombin on gap junctional (GJIC) and paracrine (PIC) intercellular communication in cultured bovine corneal endothelial cells (BCECs).

Thrombin inhibits intercellular calcium wave propagation in corneal endothelial cells by modulation of hemichannels and gap junctions.

La thrombine, une s&eacute;rine prot&eacute;ase, d&eacute;compose l&#39;int&eacute;grit&eacute; de la barri&egrave;re des cellules endoth&eacute;liales corn&eacute;ennes par la phosphorylation de la cha&icirc;ne l&eacute;g&egrave;re r&eacute;gulatrice de la myosine II (cha&icirc;ne l&eacute;g&egrave;re de la myosine ; MLC), qui induit la contractilit&eacute; du cytosquelette d&#39;actine. Cette &eacute;tude visait &agrave; examiner l&#39;effet de la thrombine sur gap jonctionnelle (CIJL) et de la communication intercellulaire paracrine (PIC) dans les cellules endoth&eacute;liales bovines cultiv&eacute;es corn&eacute;ens (BCECs).

Thrombine inhibe la propagation d&#39;ondes de calcium intercellulaire dans les cellules endoth&eacute;liales corn&eacute;ennes par modulation des jonctions h&eacute;micanaux et gap.

Trombina, una serina proteasi, rompe l&#39;integrit&agrave; della barriera delle cellule endoteliali corneale da fosforilazione della catena leggera regolamentare di miosina II (catena leggera della miosina; MLC), che induce la contrattilit&agrave; del citoscheletro di actina. Questo studio &egrave; stato intrapreso per investigare l&#39;effetto della trombina su gap giunzionali (Autoimmunit&agrave;) e paracrina (PIC) comunicazione intercellulare in cellule endoteliali corneale colte bovina (BCECs).

Trombina inibisce la propagazione dell&#39;onda intercellulare calcio nelle cellule endoteliali corneale di modulazione delle giunzioni di gap e hemichannels.

In corneal endothelial cells, intercellular Ca(2+) waves elicited by a mechanical stimulus involve paracrine intercellular communication, mediated by ATP release via connexin hemichannels, as well as gap junctional intercellular communication. Both mechanisms are inhibited by thrombin, which activates RhoA and hence results in myosin light chain phosphorylation. This study was conducted to examine the effects of adenosine, which is known to oppose thrombin-induced RhoA activation, thereby leading to myosin light chain dephosphorylation, on gap junctional intercellular communication and paracrine intercellular communication in cultured bovine corneal endothelial cells.

Adenosine opposes thrombin-induced inhibition of intercellular calcium wave in corneal endothelial cells.

Dans les cellules endoth&eacute;liales corn&eacute;ennes, intercellulaires Ca(2+) vagues d&eacute;clench&eacute;es par un stimulus m&eacute;canique impliquent la communication intercellulaire paracrine, m&eacute;di&eacute;e par lib&eacute;ration d&#39;ATP via connexin h&eacute;micanaux, ainsi que communication intercellulaire jonctions lacunaires. Ces deux m&eacute;canismes sont inhib&eacute;s par la thrombine, qui active RhoA et donc se traduit par la phosphorylation de la cha&icirc;ne l&eacute;g&egrave;re de myosine. Cette &eacute;tude visait &agrave; examiner les effets de l&#39;ad&eacute;nosine, qui est connu pour s&#39;opposer &agrave; l&#39;activation RhoA induite par la thrombine, ce qui conduirait &agrave; la d&eacute;phosphorylation de la cha&icirc;ne l&eacute;g&egrave;re de myosine, sur la communication intercellulaire jonctions lacunaires et paracrine communication intercellulaire en cellules endoth&eacute;liales corn&eacute;ennes bovines.

L&#39;ad&eacute;nosine est oppos&eacute; &agrave; l&#39;inhibition induite par la thrombine d&#39;onde calcium intercellulaire dans les cellules endoth&eacute;liales corn&eacute;ennes.

In cellule endoteliali corneali intercellulare onde Ca(2+) provocate da uno stimolo meccanico coinvolgono comunicazione intercellulare paracrina, mediata dal rilascio di ATP tramite connessina hemichannels, come pure la comunicazione intercellulare giunzionale gap. Entrambi i meccanismi sono inibiti dalla trombina, che attiva RhoA e quindi provoca la fosforilazione di catena leggera della miosina. Questo studio &egrave; stato condotto per esaminare gli effetti dell&#39;adenosina, che &egrave; noto di opporsi, in attivazione RhoA trombina-indotta, portando cos&igrave; alla defosforilazione della catena leggera della miosina, sulla comunicazione intercellulare giunzionale gap e paracrina comunicazione intercellulare in cellule endoteliali corneale bovina colte.

Adenosina si oppone l&#39;inibizione trombina-indotta dell&#39;onda intercellulare calcio nelle cellule endoteliali corneale.

Thrombin inhibits intercellular Ca(2+) wave propagation in bovine corneal endothelial cells (BCECs) through a mechanism dependent on myosin light chain (MLC) phosphorylation. In this study, blebbistatin, a selective myosin II ATPase inhibitor, was used to investigate whether the effect of thrombin is mediated by enhanced actomyosin contractility.

The myosin II ATPase inhibitor blebbistatin prevents thrombin-induced inhibition of intercellular calcium wave propagation in corneal endothelial cells.

Thrombine inhibe la propagation des ondes Ca(2+) intercellulaire dans les cellules endoth&eacute;liales corn&eacute;ennes bovines (BCECs) gr&acirc;ce &agrave; un m&eacute;canisme d&eacute;pendant de la phosphorylation de la myosine (MLC) de la cha&icirc;ne l&eacute;g&egrave;re. Dans cette &eacute;tude, blebbistatin, inhibiteur s&eacute;lectif de la myosine II ATPase, a &eacute;t&eacute; utilis&eacute; pour &eacute;tudier si l&#39;effet de la thrombine est m&eacute;di&eacute;e par la contractilit&eacute; actomyosine am&eacute;lior&eacute;e.

La myosine ATPase II inhibiteur blebbistatin emp&ecirc;che l&#39;inhibition induite par la thrombine de propagation d&#39;ondes de calcium intercellulaire dans les cellules endoth&eacute;liales corn&eacute;ennes.

Trombina inibisce la propagazione di onde Ca(2+) intercellulare in cellule endoteliali corneali bovina (BCECs) attraverso un meccanismo dipendente da fosforilazione (MLC) catena leggera della miosina. In questo studio, blebbistatin, un inibitore II ATPasi della miosina selettiva, &egrave; stato utilizzato per indagare se l&#39;effetto della trombina &egrave; mediata dalla contrattilit&agrave; actomiosina avanzata.

La miosina II ATPasi inibitore blebbistatin impedisce l&#39;inibizione trombina-indotta della propagazione dell&#39;onda intercellulare calcio nelle cellule endoteliali corneale.

Role for heparan sulfate proteoglycan in thrombin-induced calcium transients and nitric oxide production in aortic endothelial cells.

R&ocirc;le de l&#39;h&eacute;parane sulfate prot&eacute;oglycane &agrave; transitoires de calcium induite par la thrombine et de production de monoxyde d&#39;azote dans les cellules endoth&eacute;liales aortiques.

Ruolo di eparan solfato proteoglycan nei transitori di calcio trombina-indotta e la produzione di ossido nitrico nelle cellule endoteliali dell&#39;aorta.

Comunicazione intercellulare (IC) &egrave; mediata da giunzioni di gap (GJs) e hemichannels, che consistono di proteine. Questo &egrave; stato particolarmente ben documentato per la famiglia di connessina (Cx). Inizialmente, Cxs si pensava fossero le proteine unica capace di formazione GJ nei vertebrati. Circa 10 anni fa, tuttavia, una nuova famiglia della proteina formando GJ correlata a innexins invertebrati (Inxs) fu scoperto nei vertebrati e il nome della famiglia pannexin (Panx). Panxs, che sono strutturalmente simili a Cxs, ma evolutionarily distinct, hanno dimostrato di essere espressi con Cxs nei vertebrati. Entrambe le famiglie di proteine mostrano propriet&agrave; distinte e hanno la loro particolare funzione. Identificazione dei meccanismi che controllano Panx canale gating &egrave; una grande sfida per il futuro lavoro. In questa recensione, ci concentriamo sulle propriet&agrave; specifiche e ruolo del Panxs in condizioni normali e patologiche.

Pannexins, lontani parenti della famiglia connessina con specifiche funzioni cellulari?

Intercellular communication (IC) is mediated by gap junctions (GJs) and hemichannels, which consist of proteins. This has been particularly well documented for the connexin (Cx) family. Initially, Cxs were thought to be the only proteins capable of GJ formation in vertebrates. About 10 years ago, however, a new GJ-forming protein family related to invertebrate innexins (Inxs) was discovered in vertebrates, and named the pannexin (Panx) family. Panxs, which are structurally similar to Cxs, but evolutionarily distinct, have been shown to be co-expressed with Cxs in vertebrates. Both protein families show distinct properties and have their own particular function. Identification of the mechanisms that control Panx channel gating is a major challenge for future work. In this review, we focus on the specific properties and role of Panxs in normal and pathological conditions.

Pannexins, distant relatives of the connexin family with specific cellular functions?

La communication intercellulaire (IC) est v&eacute;hicul&eacute;e par les jonctions lacunaires (JL) et h&eacute;micanaux, qui se composent de prot&eacute;ines. Cela a &eacute;t&eacute; particuli&egrave;rement bien document&eacute;e pour la famille de connexines (Cx). Au d&eacute;part, Cxs &eacute;taient cens&eacute;s &ecirc;tre les seules prot&eacute;ines capables de formation GJ chez les vert&eacute;br&eacute;s. Environ 10 ans, cependant, une nouvelle famille de prot&eacute;ines formant GJ associ&eacute;e &agrave; innexins d&#39;invert&eacute;br&eacute;s (Inxs) a &eacute;t&eacute; d&eacute;couvert chez les vert&eacute;br&eacute;s et nomm&eacute;e la famille pannexine (PANXI). Panxs, qui sont structurellement similaire &agrave; la CX, mais &eacute;volutionnaires distincts, ont d&eacute;montr&eacute; d&#39;&ecirc;tre co-exprim&eacute;e avec CX chez les vert&eacute;br&eacute;s. Les deux familles de prot&eacute;ines montrent des propri&eacute;t&eacute;s distinctes et ont leur propre fonction particuli&egrave;re. Identification des m&eacute;canismes qui contr&ocirc;lent le Panx canal Gate est un d&eacute;fi majeur pour les travaux futurs. Dans cette revue, nous nous concentrons sur les propri&eacute;t&eacute;s sp&eacute;cifiques et le r&ocirc;le de Panxs dans des conditions normales et pathologiques.

Pannexins, des parents &eacute;loign&eacute;s de la famille de connexine avec fonctions cellulaires sp&eacute;cifiques ?

Stimolazione meccanica induce onde Ca(2 +) intercellulari dell&#39;endotelio corneale. La misura della propagazione dell&#39;onda &egrave; dipendente sull&#39;attivit&agrave; delle giunzioni di gap, hemichannels ed ectonucleotidases. Per definire ulteriormente l&#39;utilizzo di un modello di coltura cellulare per indagare la comunicazione intercellulare, in questo studio, noi abbiamo caratterizzato i cambiamenti nella propagazione di onde Ca(2 +) in cellule endoteliali corneali bovina con tempo prolungato nella cultura.

Comunicazione intercellulare ridotta e alterata morfologia delle cellule endoteliali corneali bovina con tempo prolungato in coltura cellulare.

Mechanical stimulation induces intercellular Ca(2 +) waves in the corneal endothelium. The extent of the wave propagation is dependent on the activity of gap junctions, hemichannels, and ectonucleotidases. To further establish the use of a cell culture model to investigate intercellular communication, in this study, we have characterized the changes in the Ca(2 +) wave propagation in bovine corneal endothelial cells with prolonged time in culture.

Reduced intercellular communication and altered morphology of bovine corneal endothelial cells with prolonged time in cell culture.

Une stimulation m&eacute;canique induit intercellulaires Ca(2 +) vagues dans l&#39;endoth&eacute;lium corn&eacute;en. L&#39;&eacute;tendue de la propagation de l&#39;onde d&eacute;pend de l&#39;activit&eacute; des jonctions lacunaires, h&eacute;micanaux et ectonucl&eacute;otidases. Pour &eacute;tablir davantage l&#39;utilisation d&#39;un mod&egrave;le de culture cellulaire pour &eacute;tudier la communication intercellulaire, dans cette &eacute;tude, nous avons caract&eacute;ris&eacute; les changements dans la propagation des ondes Ca(2 +) dans les cellules endoth&eacute;liales corn&eacute;ennes bovines avec temps prolong&eacute; dans la culture.

R&eacute;duit la communication intercellulaire et modifi&eacute;e la morphologie des cellules endoth&eacute;liales corn&eacute;ennes bovines avec un temps prolong&eacute; en culture cellulaire.

Connexin-assembled gap junctions (GJs) and hemichannels coordinate intercellular signaling processes. Although the regulation of connexins in GJs has been well characterized, the molecular determinants controlling connexin-hemichannel activity are unresolved. Here we investigated the regulation of Cx43-hemichannel activity by actomyosin contractility and intracellular [Ca(2+)] ([Ca(2+)](i)) using plasma membrane-permeable TAT peptides (100 Î¼M) designed to interfere with interactions between the cytoplasmic loop (CL) and carboxy-terminal (CT) in primary bovine corneal endothelial cells and HeLa, C6 glioma, and Xenopus oocytes ectopically expressing Cx43. Peptides corresponding to the last 10 CT aa (TAT-Cx43CT) prevented the inhibition of Cx43-hemichannel activity by contractility/high [Ca(2+)](i), whereas a reverse peptide (TAT-Cx43CTrev) did not. These effects were independent of zonula occludens-1, a cytoskeletal-associated Cx43-binding protein. In contrast, peptides corresponding to CL (TAT-L2) inhibited Cx43-hemichannel responses, whereas a mutant peptide (TAT-L2(H126K/I130N)) did not inhibit. In these assays, TAT-Cx43CT acted as a scaffold for TAT-L2 and vice versa, a finding supported by surface plasmon resonance measurements. Loop/tail interactions appeared essential for Cx43-hemichannel activity, because TAT-Cx43CT restored the activity of nonfunctional hemichannels, consisting of either Cx43 lacking the C-terminal tail (Cx43(M239)) or intact Cx43 ectopically expressed in Xenopus oocytes. We conclude that intramolecular loop/tail interactions control Cx43-hemichannel activity, laying the basis for developing hemichannel-specific blockers.

Intramolecular loop/tail interactions are essential for connexin 43-hemichannel activity.

Jonctions connexin-assembl&eacute;s (JL) h&eacute;micanaux coordonne les processus de signalisation intercellulaires. Bien que la r&eacute;glementation des connexines dans JL a &eacute;t&eacute; bien caract&eacute;ris&eacute;e, les d&eacute;terminants mol&eacute;culaires contr&ocirc;lant l&#39;activit&eacute; connexin-h&eacute;micanaux sont r&eacute;solues. Ici, nous avons &eacute;tudi&eacute; la r&eacute;gulation de l&#39;activit&eacute; de Cx43-h&eacute;micanaux de contractilit&eacute; actomyosine et intracellulaire [Ca(2+)] ([Ca(2+)](i)) utilisant des peptides TAT perm&eacute;ables &agrave; la membrane plasmique (100 &mu;M) con&ccedil;u pour g&ecirc;ner des interactions entre la boucle cytoplasmique (CL) et carboxy-terminal (CT) dans les cellules endoth&eacute;liales corn&eacute;ennes bovines primaires et HeLa, gliome C6, et des ovocytes de Xenopus exprimant de fa&ccedil;on ectopique Cx43. Peptides correspondant au dernier CT 10 aa (TAT-Cx43CT) ont emp&ecirc;ch&eacute; l&#39;inhibition de l&#39;activit&eacute; Cx43-h&eacute;micanaux de contractilit&eacute;/haute [Ca(2+)](i), contrairement &agrave; un peptide inverse (TAT-Cx43CTrev). Ces effets sont ind&eacute;pendants de la zonula occludens-1, une prot&eacute;ine de liaison Cx43 associ&eacute;es &agrave; cytosquelette. En revanche, peptides correspondant &agrave; CL (TAT-L2) inhib&eacute;e Cx43-h&eacute;micanaux r&eacute;ponses, alors qu&#39;un peptide mutant (TAT-L2(H126K/I130N)) n&#39;a pas inhib&eacute;. Ces essais, TAT-Cx43CT a agi comme un &eacute;chafaudage pour TAT-L2 et vice versa, une conclusion Appuy&eacute;e par des mesures de r&eacute;sonance plasmonique de surface. Les interactions de boucle/queue paraissait essentielles pour l&#39;activit&eacute; Cx43-h&eacute;micanaux, parce que TAT-Cx43CT r&eacute;tabli l&#39;activit&eacute; des h&eacute;micanaux non fonctionnel, consistant soit Cx43 manque la queue C-terminal (Cx43(M239)) ou intact Cx43 exprim&eacute;e de fa&ccedil;on ectopique dans des ovocytes de Xenopus. Nous concluons que les interactions intramol&eacute;culaires boucle/queue contr&ocirc;lent Cx43-h&eacute;micanaux activit&eacute;, jetant les bases pour l&#39;&eacute;laboration des bloqueurs de h&eacute;micanaux sp&eacute;cifiques.

Les interactions intramol&eacute;culaires boucle/queue sont essentielles pour la connexine 43-h&eacute;micanaux activit&eacute;.

Giunzioni di gap assemblato connessina (GJs) e hemichannels coordinare i processi di segnalazione intercellulari. Anche se il regolamento di connexins in GJs &egrave; stata ben caratterizzato, i determinanti molecolari connessina-hemichannel attivit&agrave; di controllo sono irrisolti. Qui abbiamo studiato il regolamento delle attivit&agrave; Cx43-hemichannel di contrattilit&agrave; actomiosina e intracellulare [Ca(2+)] ([Ca(2+)](i)) usando i peptidi TAT plasma membrana permeabile (100 &mu;M) progettati per interferire con le interazioni tra loop citoplasmatico (CL) e carbossi-terminale (CT) in cellule endoteliali corneale bovina primarie e HeLa, glioma C6, e ovociti di Xenopus ectopically esprimendo Cx43. peptidi corrispondenti agli ultimi 10 CT aa (TAT-Cx43CT) ha impedito l&#39;inibizione dell&#39;attivit&agrave; Cx43-hemichannel di contrattilit&agrave;/alto [Ca(2+)](i), considerando che non ha un inverso peptide (TAT-Cx43CTrev). Questi effetti sono stati indipendenti della zonula occludens-1, una proteina Cx43-associazione citoscheletrici associati. Al contrario, peptidi corrispondenti a CL (TAT-L2) inibito Cx43-hemichannel risposte, considerando che un peptide mutante (non inibiscono la TAT-L2(H126K/I130N)). In questi saggi, TAT-Cx43CT ag&igrave; come un&#39;impalcatura per TAT-L2 e viceversa, una constatazione supportata da misure di risonanza plasmonica di superficie. Interazioni loop/coda apparvero essenziale per attivit&agrave; Cx43-hemichannel, perch&eacute; TAT-Cx43CT ripristinata l&#39;attivit&agrave; di hemichannels non funzionante, costituiti entrambi Cx43 manca la coda C-terminale (Cx43(M239)) o intatto Cx43 ectopically espressa in ovociti di Xenopus. Concludiamo che le interazioni intramolecolari loop/coda controllano Cx43-hemichannel attivit&agrave;, gettando le basi per lo sviluppo di specifiche hemichannel bloccanti.

Interazioni intramolecolari loop/coda sono essenziali per la connessina 43-hemichannel attivit&agrave;.

The pannexin (Panx) family of proteins, which is co-expressed with connexins (Cxs) in vertebrates, was found to be a new GJ-forming protein family related to invertebrate innexins. During the past ten years, different studies showed that Panxs mainly form hemichannels in the plasma membrane and mediate paracrine signalling by providing a flux pathway for ions such as CaÂ²(+), for ATP and perhaps for other compounds, in response to physiological and pathological stimuli. Although the physiological role of Panxs as a hemichannel was questioned, there is increasing evidence that Panx play a role in vasodilatation, initiation of inflammatory responses, ischemic death of neurons, epilepsy and in tumor suppression. Moreover, it is intriguing that Panxs may also function at the endoplasmic reticulum (ER) as intracellular CaÂ²(+)-leak channel and may be involved in ER-related functions. Although the physiological significance and meaning of such Panx-regulated intracellular CaÂ²(+) leak requires further exploration, this functional property places Panx at the centre of many physiological and pathophysiological processes, given the fundamental role of intracellular CaÂ²(+) homeostasis and dynamics in a plethora of physiological processes. In this review, we therefore want to focus on Panx as channels at the plasma membrane and at the ER membranes with a particular emphasis on the potential implications of the latter in intracellular CaÂ²(+) signalling.

Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum.

La famille de pannexine (PANXI) des prot&eacute;ines, ce qui est co-exprim&eacute;e avec les connexines (CX) chez les vert&eacute;br&eacute;s, s&#39;est av&eacute;r&eacute;e pour &ecirc;tre une nouvelle famille de prot&eacute;ines formant GJ associ&eacute;e &agrave; innexins d&#39;invert&eacute;br&eacute;s. Au cours des dix derni&egrave;res ann&eacute;es, diff&eacute;rentes &eacute;tudes ont montr&eacute; que les Panxs formaient principalement h&eacute;micanaux dans la membrane plasmique et m&eacute;diate paracrine signalisation en fournissant une voie de flux d&#39;ions tels que Ca&sup2;(+), pour l&#39;ATP et peut-&ecirc;tre d&#39;autres compos&eacute;s, en r&eacute;ponse &agrave; des stimuli physiologiques et pathologiques. Bien que le r&ocirc;le physiologique de Panxs comme un h&eacute;micanaux a &eacute;t&eacute; mise en doute, il y a des preuves croissantes que Panx joue un r&ocirc;le dans la vasodilatation, l&#39;initiation des r&eacute;ponses inflammatoires, isch&eacute;mique mort neuronale, l&#39;&eacute;pilepsie et dans la suppression tumorale. En outre, il est curieux que Panxs peut &eacute;galement servir au r&eacute;ticulum endoplasmique (re) Ca&sup2; intracellulaire (+)-canal de fuite et pourraient &ecirc;tre impliqu&eacute;s dans des fonctions li&eacute;es &agrave; l&#39;ER. Bien que la signification physiologique et la signification de ce r&eacute;glement&eacute;s Panx intracellulaire Ca&sup2;(+) fuite exige davantage exploration, cette propri&eacute;t&eacute; fonctionnelle place Panx au centre de nombreux processus physiologiques et physiopathologiques, &eacute;tant donn&eacute; le r&ocirc;le fondamental de l&#39;hom&eacute;ostasie intracellulaire de Ca&sup2;(+) et de la dynamique dans une multitude de processus physiologiques. Dans cette revue, nous voulons donc se concentrer sur Panx comme canaux &agrave; la membrane plasmique et les membranes ER avec un accent particulier sur les cons&eacute;quences potentielles de ce dernier en signalisation intracellulaire de Ca&sup2;(+).

Canaux pannexine dans le communiqu&eacute; de l&#39;ATP et au-del&agrave; : un rendez-vous inattendu au r&eacute;ticulum endoplasmique.

La famiglia pannexin (Panx) delle proteine, che &egrave; espressi con connexins (Cxs) nei vertebrati, &egrave; stata trovata per essere una nuova famiglia della proteina formando GJ correlata a innexins invertebrati. Negli ultimi dieci anni, diversi studi hanno dimostrato che Panxs formano principalmente hemichannels nella membrana plasmatica e mediata paracrina segnalazione fornendo un percorso di flusso di ioni quali Ca&sup2;(+), trifosfato di Adenosina e forse per altri composti, in risposta a stimoli fisiologici e patologici. Anche se &egrave; stato messo in discussione il ruolo fisiologico di Panxs come un hemichannel, c&#39;&egrave; crescente evidenza che Panx gioca un ruolo nella vasodilatazione, iniziazione di risposte infiammatorie, ischemico morte dei neuroni, epilessia e nella soppressione del tumore. Inoltre, &egrave; intrigante che Panxs pu&ograve; anche funzionare nel reticolo endoplasmatico (ER) come Ca&sup2; intracellulare (+)-perdita di canale e possono essere coinvolte in funzioni di ER. Anche se il significato fisiologico e il significato di tale perdita Ca&sup2;(+) intracellulare regolamentati Panx richiede ulteriore esplorazione, questa propriet&agrave; funzionale posti Panx al centro di molti processi fisiologici e fisiopatologici, dato il ruolo fondamentale di omeostasi intracellulare di Ca&sup2;(+) e dinamiche in una miriade di processi fisiologici. In questa recensione, vogliamo quindi mettere a fuoco su Panx come canali presso la membrana plasmatica e le membrane ER con una particolare attenzione per le potenziali implicazioni di quest&#39;ultimo in Ca&sup2;(+) di segnalazione intracellulare.

Pannexin canali nel rilascio di ATP e oltre: un inaspettato appuntamento al reticolo endoplasmatico.

It is nowadays well established that gap junctions are critical gatekeepers of cell proliferation, by controlling the intercellular exchange of essential growth regulators. In recent years, however, it has become clear that the picture is not as simple as originally anticipated, as structural precursors of gap junctions can affect cell cycling by performing actions not related to gap junctional intercellular communication. Indeed, connexin hemichannels also foresee a pathway for cell growth communication, albeit between the intracellular compartment and the extracellular environment, while connexin proteins as such can directly or indirectly influence the production of cell cycle regulators independently of their channel activities. Furthermore, a novel set of connexin-like proteins, the pannexins, have lately joined in as regulators of the cell proliferation process, which they can affect as either single units or as channel entities. In the current paper, these multifaceted aspects of connexin-related signalling in cell cycling are reviewed.

Connexins: sensors and regulators of cell cycling.

Il est aujourd&#39;hui bien &eacute;tabli que les jonctions sont critiques portiers de la prolif&eacute;ration cellulaire, en contr&ocirc;lant les &eacute;changes intercellulaires de r&eacute;gulateurs de croissance essentiel. Ces derni&egrave;res ann&eacute;es, cependant, il est devenu clair que l&#39;image n&#39;est pas aussi simple qu&#39;initialement pr&eacute;vu, comme pr&eacute;curseurs structurelles des jonctions lacunaires peuvent affecter la cellule cyclisme en effectuant des actions non li&eacute;es &agrave; la communication intercellulaire jonctions lacunaires. En effet, h&eacute;micanaux connexin pr&eacute;voit aussi une voie de communication de cellule de croissance, quoique entre le compartiment intracellulaire et le milieu extracellulaire, tandis que les prot&eacute;ines connexines comme tel peuvent directement ou indirectement influencent la production de r&eacute;gulateurs de cycle cellulaire ind&eacute;pendamment de leurs activit&eacute;s de canal. En outre, un ensemble roman de connexin-comme les prot&eacute;ines, les pannexins, ont r&eacute;cemment rejoint comme r&eacute;gulateurs du processus de prolif&eacute;ration cellulaire, qui qu&#39;elles n&#39;atteignent que deux unit&eacute;s simples ou en tant qu&#39;entit&eacute;s de canal. Dans le pr&eacute;sent document, ces aspects multiformes de connexin-associ&eacute;s de signalisation dans cellule cyclisme sont pass&eacute;s en revue.

Connexines : capteurs et r&eacute;gulateurs cellule de cyclisme.

Che &egrave; oggi ben accertato che giunzioni di gap critico gatekeeper della proliferazione cellulare, controllando lo Scambio intercellulare di regolatori di crescita essenziali. Negli ultimi anni, tuttavia, &egrave; diventato chiaro che l&#39;immagine non &egrave; semplice come originariamente previsto, come precursori strutturali delle giunzioni di gap possono influire sulla cella ciclismo eseguendo azioni non legate alla comunicazione intercellulare giunzionale gap. Infatti, connessina hemichannels prevedono anche un percorso per la comunicazione di crescita delle cellule, anche se tra il compartimento intracellulare e l&#39;ambiente extracellulare, mentre connessina proteine come tale pu&ograve; direttamente o indirettamente influenzano la produzione di regolatori del ciclo cellulare indipendentemente dalla loro attivit&agrave; di canale. Inoltre, un romanzo insieme di connessina-come le proteine, il pannexins, ultimamente hanno aderito come regolatori del processo di proliferazione delle cellule, che possono interessare come una singola unit&agrave; oppure come entit&agrave; di canale. Nel documento corrente, questi aspetti multiformi della connessina relative segnalazione cella in bicicletta sono rivisti.

Connexins: sensori e regolatori di cella in bicicletta.

ATP-dependent paracrine signaling, mediated via the release of ATP through plasma membrane-embedded hemichannels of the connexin family, coordinates a synchronized response between neighboring cells. Connexin 43 (Cx43) hemichannels that are present in the plasma membrane need to be tightly regulated to ensure cell viability. In monolayers of bovine corneal endothelial cells (BCEC),Cx43-mediated ATP release is strongly inhibited when the cells are treated with inflammatory mediators, in particular thrombin and histamine. In this study we investigated the involvement of RhoA activation in the inhibition of hemichannel-mediated ATP release in BCEC. We found that RhoA activation occurs rapidly and transiently upon thrombin treatment of BCEC. The RhoA activity correlated with the onset of actomyosin contractility that is involved in the inhibition of Cx43 hemichannels. RhoA activation and inhibition of Cx43-hemichannel activity were both prevented by pre-treatment of the cells with C3-toxin as well as knock down of RhoA by siRNA. These findings provide evidence that RhoA activation is a key player in thrombin-induced inhibition of Cx43-hemichannel activity. This study demonstrates that RhoA GTPase activity is involved in the acute inhibition of ATP-dependent paracrine signaling, mediated by Cx43 hemichannels, in response to the inflammatory mediator thrombin. Therefore, RhoA appears to be an important molecular switch that controls Cx43 hemichannel openings and hemichannel-mediated ATP-dependent paracrine intercellular communication under (patho)physiological conditions of stress.

RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.

ATP-d&eacute;pendante paracrine signalisation, m&eacute;di&eacute;e par la lib&eacute;ration d&#39;ATP par le biais de h&eacute;micanaux int&eacute;gr&eacute;e &agrave; la membrane plasmique de la famille de connexine, coordonne une r&eacute;ponse synchronis&eacute;e entre les cellules voisines. H&eacute;micanaux connexine 43 (Cx43) qui sont pr&eacute;sents dans la membrane de plasma doivent &ecirc;tre &eacute;troitement contr&ocirc;l&eacute;e afin d&#39;assurer la viabilit&eacute; des cellules. En monocouches de cellules endoth&eacute;liales corn&eacute;ennes bovines (BCEC), communiqu&eacute; de la m&eacute;diation Cx43 ATP est fortement inhib&eacute;e lorsque les cellules sont trait&eacute;es avec les m&eacute;diateurs de l&#39;inflammation, en particulier thrombine et de l&#39;histamine. Dans cette &eacute;tude, nous avons examin&eacute; l&#39;implication de l&#39;activation de RhoA dans l&#39;inhibition de la lib&eacute;ration d&#39;ATP h&eacute;micanaux m&eacute;diation dans BCEC. Nous avons trouv&eacute; que RhoA activation se produit rapidement et transitoirement par traitement de thrombine de BCEC. L&#39;activit&eacute; de RhoA corr&eacute;l&eacute;e avec l&#39;apparition de la contractilit&eacute; actomyosine qui est impliqu&eacute;e dans l&#39;inhibition de la Cx43 h&eacute;micanaux. RhoA activation et inhibition de l&#39;activit&eacute; Cx43-h&eacute;micanaux ont &eacute;t&eacute; tous deux emp&ecirc;ch&eacute;s par pr&eacute;traitement des cellules avec la toxine C3 ainsi que knock down de RhoA de siARN. Ces r&eacute;sultats fournissent la preuve que l&#39;activation de RhoA est un acteur cl&eacute; dans inhibition induite par la thrombine de Cx43-h&eacute;micanaux. Cette &eacute;tude d&eacute;montre que l&#39;activit&eacute; RhoA GTPase est impliqu&eacute;e dans l&#39;inhibition aigu&euml; de paracrine ATP-d&eacute;pendante de signalisation, m&eacute;di&eacute;e par Cx43 h&eacute;micanaux, en r&eacute;ponse &agrave; la thrombine m&eacute;diateur inflammatoire. RhoA semble donc &ecirc;tre un interrupteur mol&eacute;culaire important qui contr&ocirc;le Cx43 h&eacute;micanaux ouvertures et la m&eacute;diation h&eacute;micanaux ATP-d&eacute;pendante paracrine communication intercellulaire dans des conditions physiologiques du stress (patho).

RhoA GTPase interrupteur commande Cx43-h&eacute;micanaux activit&eacute; &agrave; travers le syst&egrave;me contractile.

Segnalazione paracrina ATP-dipendente, mediata attraverso il rilascio di ATP attraverso la membrana plasmatica-embedded hemichannels della famiglia connessina, coordina una risposta sincronizzata tra cellule vicine. Hemichannels connessina 43 (Cx43) che sono presenti nella membrana del plasma devono essere strettamente regolato per garantire la vitalit&agrave; delle cellule. In monostrati di cellule endoteliali corneali bovina (BCEC), rilascio di ATP Cx43-mediata &egrave; fortemente inibito quando le cellule sono trattate con mediatori infiammatori, in particolare trombina e l&#39;istamina. In questo studio abbiamo valutato il coinvolgimento di RhoA attivazione nell&#39;inibizione del rilascio di ATP hemichannel-mediata in BCEC. Abbiamo trovato che RhoA attivazione si verifica rapidamente e transitoriamente previo trattamento di trombina di BCEC. L&#39;attivit&agrave; di RhoA correlato con l&#39;insorgenza di contrattilit&agrave; actomiosina che &egrave; coinvolta nell&#39;inibizione di Cx43 hemichannels. RhoA attivazione e inibizione dell&#39;attivit&agrave; Cx43-hemichannel entrambi sono stati evitati dal pretrattamento delle cellule con C3-tossina, nonch&eacute; abbattere di RhoA di siRNA. Questi risultati forniscono la prova che l&#39;attivazione RhoA &egrave; un giocatore chiave nella inibizione trombina-indotta di Cx43-hemichannel attivit&agrave;. Questo studio dimostra che attivit&agrave; RhoA GTPase &egrave; coinvolto nell&#39;inibizione acuta del trifosfato di Adenosina-dipendente paracrina di segnalazione, mediata da hemichannels Cx43, in risposta alla trombina mediatore infiammatorio. Pertanto, RhoA sembra essere un importante interruttore molecolare che controlla Cx43 hemichannel aperture e hemichannel-mediata trifosfato di Adenosina-dipendente paracrina comunicazione intercellulare in condizioni fisiologiche (patho) dello stress.

RhoA GTPase interruttore controlla Cx43-hemichannel attivit&agrave; attraverso il sistema contrattile.

Connexin 43 (Cx43)-hemichannel activity is controlled by intramolecular interactions between cytoplasmic loop and C-terminal tail. We previously identified the last 10 amino acids of the C-terminal tail of Cx43 as essential for Cx43-hemichannel activity. We developed a cell-permeable peptide covering this sequence (TAT-Cx43CT). In this study, we examined the critical molecular determinants in TAT-Cx43CT to restore Cx43-hemichannel activity. Using amino acid substitutions in TAT-Cx43CT, we identified the two aspartate (Asp378 and Asp379) and two proline (Pro375 and Pro377) residues as critical for TAT-Cx43CT activity, since TAT-Cx43CT(DD/AA) and TAT-Cx43CT(PP/GG) did not overcome the inhibition of Cx43-hemichannel activity induced by thrombin, micromolar cytoplasmic Ca(2+) concentration or truncation of Cx43 at M(239). Consistent with this, we found that biotin-Cx43CT(DD/AA) was much less efficient than biotin-Cx43CT to bind the purified CL domain of Cx43 in surface plasmon resonance experiments. In conclusion, we postulate that Asp378 and Asp379 in the C-terminal part of Cx43 are essential for loop/tail interactions in Cx43 hemichannels, while Pro375 and Pro377 may help to properly coordinate the critical Asp residues.

Negatively charged residues (Asp378 and Asp379) in the last ten amino acids of the C-terminal tail of Cx43 hemichannels are essential for loop/tail interactions.

Connexine 43 (Cx43)-h&eacute;micanaux activit&eacute; est contr&ocirc;l&eacute;e par des interactions intramol&eacute;culaires entre boucle cytoplasmique et queue C-terminal. Nous avons d&eacute;j&agrave; identifi&eacute; les 10 derniers acides amin&eacute;s de la queue de C-terminal de Cx43 comme essentielle pour l&#39;activit&eacute; Cx43-h&eacute;micanaux. Nous avons d&eacute;velopp&eacute; un peptide cellulaire perm&eacute;able couvrant cette s&eacute;quence (TAT-Cx43CT). Dans cette &eacute;tude, nous examinons les d&eacute;terminants mol&eacute;culaires critiques en TAT-Cx43CT pour restaurer l&#39;activit&eacute; Cx43-h&eacute;micanaux. &Agrave; l&#39;aide des substitutions d&#39;acides amin&eacute;s dans le TAT-Cx43CT, nous avons identifi&eacute; l&#39;aspartate deux (Asp378 et Asp379) et deux r&eacute;sidus de proline (Pro375 et Pro377) comme critiques pour l&#39;activit&eacute; de TAT-Cx43CT, car TAT-Cx43CT(DD/AA) et TAT-Cx43CT(PP/GG) n&#39;a pas surmont&eacute; l&#39;inhibition de l&#39;activit&eacute; Cx43-h&eacute;micanaux induite par la thrombine, micromolaire concentration cytoplasmique de Ca(2+) ou la troncation des Cx43 &agrave; M(239). Conform&eacute;ment &agrave; cela, nous avons constat&eacute; que biotin-Cx43CT(DD/AA) &eacute;tait beaucoup moins efficace que la biotine-Cx43CT pour lier le domaine purifi&eacute; de CL de Cx43 dans les exp&eacute;riences de r&eacute;sonance plasmonique de surface. En conclusion, nous postulons que Asp378 et Asp379 dans la partie C-terminale de Cx43 sont essentiels pour les interactions de la boucle/queue en Cx43 h&eacute;micanaux, tandis que Pro375 et Pro377 peuvent aider &agrave; coordonner correctement les r&eacute;sidus Asp critiques.

R&eacute;sidus charg&eacute;s n&eacute;gativement (Asp378 et Asp379) dans les dix derniers acides amin&eacute;s de la queue de C-terminal de Cx43 h&eacute;micanaux sont essentielles pour les interactions de la boucle/queue.

Connessina 43 (Cx43)-hemichannel attivit&agrave; &egrave; controllata da interazioni intramolecolari tra loop citoplasmatico e coda C-terminale. Abbiamo identificato in precedenza gli ultimi 10 amminoacidi della coda C-terminale di Cx43 come essenziale per attivit&agrave; Cx43-hemichannel. Abbiamo sviluppato un cellula permeabile del peptide che coprono questa sequenza (TAT-Cx43CT). In questo studio, abbiamo esaminato i determinanti molecolari critici in TAT-Cx43CT per ripristinare Cx43-hemichannel attivit&agrave;. Utilizzando le sostituzioni dell&#39;amminoacido in TAT-Cx43CT, abbiamo identificato i due aspartato (Asp378 e Asp379) e due residui prolina (Pro375 e Pro377) come critica per l&#39;attivit&agrave; di TAT-Cx43CT, dal TAT-Cx43CT(DD/AA) e TAT-Cx43CT(PP/GG) non ha fatto superare l&#39;inibizione dell&#39;attivit&agrave; Cx43-hemichannel indotta da trombina, micromolare concentrazione citoplasmatica di Ca(2+) o il troncamento di Cx43 presso M(239). Coerentemente con questo, abbiamo trovato che biotin-Cx43CT(DD/AA) era molto meno efficiente che biotina-Cx43CT per associare il dominio CL purificato di Cx43 in esperimenti di risonanza plasmonica di superficie. In conclusione, abbiamo postulato che Asp378 e Asp379 nella parte C-terminale della Cx43 sono essenziali per le interazioni del ciclo/coda in Cx43 hemichannels, mentre Pro375 e Pro377 possono aiutare a coordinare correttamente i critici residui Asp.

Residui caricati negativamente (Asp378 e Asp379) negli ultimi dieci amminoacidi della coda C-terminale di Cx43 hemichannels sono essenziali per le interazioni loop/coda.

About a decade ago, the molecular determinants controlling the opening and closing of Cx43 gap junction channels have been identified. Advanced biophysical approaches revealed a critical role for structural rearrangements in the cytoplasmic loop and dimerization of the C-terminal tail, resulting in binding of the C-terminal tail to the cytoplasmic loop and Cx43 gap junction channel closure during cellular acidosis. This has spurred the development of Cx43-mimetic peptides and peptidomimetics that interfere with these loop/tail interactions, thereby preventing the closure of Cx43 gap junctions, e.g. in the heart upon ischemia. Recently, we found that loop/tail interactions control Cx43-hemichannel activity but with an opposite effect. Binding of the C-terminal tail to the cytoplasmic loop is a requisite for the opening of Cx43 hemichannels in response to different stimuli, like decreased extracellular [Ca(2+)], increased intracellular [Ca(2+)], positive membrane potentials or ischemia. Strikingly, peptides that favor the open state of Cx43 gap junctions like the L2 peptide inhibit Cx43-hemichannel opening. These tools now provide unprecedented opportunities to selectively inhibit Cx43 hemichannels while maintaining Cx43 gap junction communication, impossible to achieve with siRNA or knockdown approaches both affecting gap junctions and hemichannels. These tools not only are very helpful to unravel the role of Cx43 hemichannels in complex biological systems, but also hold therapeutic potential to counteract excessive Cx43-hemichannel activity like in ischemia/reperfusion in the brain and the heart or to prevent Cx43 hemichannel-mediated gliotransmitter release in the basal amygdala during memory consolidation in response to emotional events. This article is part of a Special Issue entitled 'Connexin based channels'.

Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: Gap junctions versus hemichannels.

Il y a une dizaine d&#39;ann&eacute;es, les d&eacute;terminants mol&eacute;culaires contr&ocirc;lant l&#39;ouverture et la fermeture des canaux de jonction gap Cx43 ont &eacute;t&eacute; identifi&eacute;s. Approches biophysiques avanc&eacute;s a r&eacute;v&eacute;l&eacute; un r&ocirc;le critique pour les r&eacute;arrangements structuraux dans la boucle cytoplasmique et la dim&eacute;risation de la queue de C-terminal, r&eacute;sultant dans la fixation de la queue de C-terminal &agrave; la boucle cytoplasmique et la fermeture du chenal Cx43 gap junction lors d&#39;une acidose cellulaire. Ceci a stimul&eacute; le d&eacute;veloppement de peptides Cx43-mim&eacute;tiques et boucle/queue de peptidomimetics qui interf&egrave;rent avec ces interactions, ce qui emp&ecirc;che la fermeture de Cx43 jonctions, par exemple dans le c&oelig;ur &agrave; l&#39;isch&eacute;mie. R&eacute;cemment, nous avons trouv&eacute; que les interactions de boucle/queue contr&ocirc;lent l&#39;activit&eacute; de Cx43-h&eacute;micanaux mais avec un effet inverse. Fixation de la queue de C-terminale de la boucle cytoplasmique est requise pour l&#39;ouverture de Cx43 h&eacute;micanaux en r&eacute;ponse &agrave; diff&eacute;rents stimuli, comme une diminution extracellulaire [Ca(2+)], une augmentation intracellulaire [Ca(2+)], potentiels de membrane positive ou isch&eacute;mie. Remarquablement, les peptides qui favorisent l&#39;&eacute;tat ouvert de jonctions Cx43 comme la L2 peptides inhibent Cx43-h&eacute;micanaux d&#39;ouverture. Ces outils fournissent maintenant des possibilit&eacute;s sans pr&eacute;c&eacute;dent d&#39;inhiber s&eacute;lectivement Cx43 h&eacute;micanaux tout en conservant les Cx43 communication jonctions gap, impossible &agrave; r&eacute;aliser avec les siARN ou choc s&#39;approche influant sur la jonctions lacunaires et l&#39;h&eacute;micanaux. Ces outils sont non seulement tr&egrave;s utiles pour d&eacute;m&ecirc;ler le r&ocirc;le de Cx43 h&eacute;micanaux dans les syst&egrave;mes biologiques complexes, mais aussi d&eacute;tenir un potentiel th&eacute;rapeutique pour neutraliser l&#39;activit&eacute; excessive de Cx43-h&eacute;micanaux comme en isch&eacute;mie/reperfusion dans le cerveau et le coeur, ou pour emp&ecirc;cher Cx43 h&eacute;micanaux-mediated gliotransmetteurs lib&eacute;rer dans l&#39;amygdale basale au cours de la consolidation de la m&eacute;moire en r&eacute;ponse aux &eacute;v&eacute;nements &eacute;motionnels. Cet article fait partie d&#39;un num&eacute;ro sp&eacute;cial intitul&eacute; &#39;Inspir&eacute;es de la connexine canaux&#39;.

Peptides et peptides d&eacute;riv&eacute;s de mol&eacute;cules ciblant les domaines intracellulaires de Cx43 : Gap jonctions contre h&eacute;micanaux.

Connexin (Cx) and pannexin (Panx) proteins form large conductance channels, which function as regulators of communication between neighboring cells via gap junctions and/or hemichannels. Intercellular communication is essential to coordinate cellular responses in tissues and organs, thereby fulfilling an essential role in the spreading of signaling, survival and death processes. The functional properties of gap junctions and hemichannels are modulated by different physiological and pathophysiological stimuli. At the molecular level, Cxs and Panxs function as multi-protein channel complexes regulating their channel localization and activity. In addition to this, gap junctional channels and hemichannels are modulated by different post-translational modifications, including phosphorylation, glycosylation, proteolysis, N-acetylation, S-nitrosylation, ubiquitination, lipidation, hydroxylation, methylation and deamidation. These PTMs influence almost all aspects of communicating junctional channels in normal cell biology and pathophysiology. In this review, we will provide a systematic overview of PTMs of communicating junction proteins and discuss their effects on Cx and Panx-channel activity and localization. This article is protected by copyright. All rights reserved.

Regulation of connexin- and pannexin-based channels by post-translational modifications.

Connexine (Cx) et pannexine (PANXI) prot&eacute;ines forment des canaux de grande conductance, qui servent de r&eacute;gulateurs de communication entre les cellules voisines via les jonctions lacunaires et/ou h&eacute;micanaux. La communication intercellulaire est essentielle pour coordonner les r&eacute;ponses cellulaires dans les tissus et organes, remplissant ainsi un r&ocirc;le essentiel dans la diffusion de la signalisation, les processus de survie et de la mort. Les propri&eacute;t&eacute;s fonctionnelles des jonctions lacunaires et h&eacute;micanaux sont modul&eacute;es par diff&eacute;rents stimuli physiologiques et physiopathologiques. Au niveau mol&eacute;culaire, Cxs et Panxs fonctionnent sous forme de complexes multi-prot&eacute;ine canal r&eacute;glementer leurs activit&eacute;s et localisation de canal. En outre, h&eacute;micanaux et canaux jonctions gap est modul&eacute;s par diff&eacute;rentes modifications post-traductionnelles, y compris la phosphorylation, glycosylation, prot&eacute;olyse, N-ac&eacute;tylation, S-nitrosylation, ubiquitination, lipidation, hydroxylation, m&eacute;thylation et d&eacute;samidation. Ces SPTM influence presque tous les aspects de la communication jonctionnelle canaux en biologie cellulaire normale et physiopathologie. Dans cette revue, nous fournirons un aper&ccedil;u syst&eacute;matique des SPTM de communiquer des prot&eacute;ines de jonction et discuter de leurs effets sur l&#39;activit&eacute; Cx et Panx-canal et de la localisation. Cet article est prot&eacute;g&eacute; par copyright. Tous droits r&eacute;serv&eacute;s.

Article	Year
Thrombin inhibits intercellular calcium wave propagation in corneal endothelial cells by modulation of hemichannels and gap junctions. Investigative ophthalmology & visual science\| PubMed ID: 17197525	2007
Adenosine opposes thrombin-induced inhibition of intercellular calcium wave in corneal endothelial cells. Investigative ophthalmology & visual science\| PubMed ID: 17389480	2007
The myosin II ATPase inhibitor blebbistatin prevents thrombin-induced inhibition of intercellular calcium wave propagation in corneal endothelial cells. Investigative ophthalmology & visual science\| PubMed ID: 18614806	2008
Role for heparan sulfate proteoglycan in thrombin-induced calcium transients and nitric oxide production in aortic endothelial cells. Thrombosis and haemostasis\| PubMed ID: 18766250	2008
Pannexins, distant relatives of the connexin family with specific cellular functions? BioEssays : news and reviews in molecular, cellular and developmental biology\| PubMed ID: 19644918	2009
Reduced intercellular communication and altered morphology of bovine corneal endothelial cells with prolonged time in cell culture. Current eye research\| PubMed ID: 19899980	2009
Intramolecular loop/tail interactions are essential for connexin 43-hemichannel activity. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 20634352	2010
Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum. Cellular signalling\| PubMed ID: 20688156	2011
Connexins: sensors and regulators of cell cycling. Biochimica et biophysica acta\| PubMed ID: 20801193	2011
RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system. PloS one\| PubMed ID: 22860057	2012
Negatively charged residues (Asp378 and Asp379) in the last ten amino acids of the C-terminal tail of Cx43 hemichannels are essential for loop/tail interactions. Biochemical and biophysical research communications\| PubMed ID: 23376080	2013
Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: Gap junctions versus hemichannels. Neuropharmacology\| PubMed ID: 23664811	2013
Regulation of connexin- and pannexin-based channels by post-translational modifications. Biology of the cell / under the auspices of the European Cell Biology Organization\| PubMed ID: 23718186	2013

Catheleyne D'hondt

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