Name: cadherins guide cell sorting in tissues
Uploaded: 2023-04-30T11:55:30.000Z
Duration: 1 min 19 s
Channel: JoVE

Le caderine, una classe di molecole di adesione cellulare, mediano l'adesione selettiva tra le cellule e quindi svolgono un ruolo cruciale nella creazione e nel mantenimento delle strutture tissutali.
Durante lo sviluppo, le cellule indifferenziate esprimono caderine specifiche sulla loro superficie mentre si differenziano in tipi di tessuto distinti, come le caderine E sulle cellule epiteliali e le N-caderine sui neuroni.
Poiché le caderine generalmente legano altre caderine dello stesso tipo, le cellule possono aderire selettivamente l'una all'altra.
Inoltre, le cellule che esprimono livelli più elevati di caderina segregano da quelle con livelli più bassi.
Pertanto, sia la specificità quantitativa che qualitativa delle caderine aiuta a smistare e organizzare le cellule in tessuti.
Al contrario, la sottoregolazione dell'espressione della caderina porta alla perdita di adesione cellulare.
Ad esempio, le cellule tumorali che smettono di esprimere caderine possono staccarsi dalle cellule vicine e superare i vincoli tissutali.
Questa transizione, chiamata transizione da epiteliale a mesenchimale o EMT, è un passaggio essenziale nella progressione delle cellule tumorali verso le cellule maligne.

<ol>
	<li>Paulson, Alicia F., et al. "Regolazione dell'espressione della caderina nello sviluppo del sistema nervoso". Adesione e migrazione cellulare 8.1 (2014): 19-28.</li>
	<li>Berx, Geert e Frans Van Roy. "Coinvolgimento dei membri della superfamiglia della caderina nel cancro". Prospettive di Cold Spring Harbor in biologia 1.6 (2009): a003129.</li>
</ol>

caderine nell'organizzazione dei tessuti

Cadherins in Tissue Organization

Le caderine sono una superfamiglia di molecole di adesione cellulare comprendente oltre 180 varianti, con tessuti specifici che esprimono una particolare combinazione di tipi di caderine. Le caderine generalmente mostrano un legame omofilo; cioè, le caderine su una cellula si legano alle caderine dello stesso tipo o strettamente correlate su un'altra cellula. Pertanto, le cellule dello stesso tipo hanno un'affinità specifica per legarsi tra loro e raggrupparsi per formare i tessuti.

Ordinamento delle celle durante lo sviluppo

Lo smistamento cellulare svolge un ruolo essenziale durante l'embriogenesi e lo sviluppo, come dimostrato dai primi esperimenti con embrioni di anfibi. Le cellule di giovani embrioni sono state dissociate e lasciate mescolare. Quando questa miscela veniva lasciata aggregare, cellule simili si raggruppavano insieme, formando strutture. Queste strutture somigliavano a strati embrionali come il mesoderma, l'epidermide e il tubo neurale. L'espressione della caderina cambia man mano che le cellule si differenziano durante lo sviluppo, consentendo la formazione di strutture complesse come il tubo neurale dei vertebrati. Quando il solco neurale si forma dallo strato ectodermico, le cellule della placca neurale spostano la loro espressione caderina da E-caderina a N-caderina. Le cellule al confine della placca neurale iniziano ad esprimere anche altre caderine come la caderina 6B, riunendo così le due estremità e facilitando il distacco del tubo neurale.

Caderine e malignità

L'adesione cellula-cellula mediata dalla caderina è un meccanismo importante che mantiene l'omeostasi dei tessuti negli organismi multicellulari. Nei tessuti cancerosi, tuttavia, questa adesione cellulare si rompe. Molte cellule tumorali epiteliali smettono di esprimere le molecole di E-caderina, parzialmente o interamente, aiutate da vari regolatori della trascrizione. Ad esempio, un regolatore della trascrizione chiamato Twist inibisce l’espressione della E-caderina, impedendo così alle cellule tumorali di aderire alle cellule vicine. Questa trasformazione è chiamata transizione epiteliale-mesenchimale (EMT). È una caratteristica della progressione verso la malignità che consente alle cellule tumorali di fuggire e invadere altri tessuti. Il blocco sperimentale di Twist nelle cellule maligne del cancro al seno riduce la loro malignità. Al contrario, le cellule epiteliali normali possono essere indotte a sottoporsi a EMT aumentando l'espressione di Twist.

Caderine nell'organizzazione dei tessuti

Le caderine sono una superfamiglia di molecole di adesione cellulare comprendente oltre 180 varianti, con tessuti specifici che esprimono una particolare combinazione di ...

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cadherins guide cell sorting in tissues

Cadherins help cells sort into the right tissues during development. They are a large superfamily of cell adhesion molecules, with more than 180 variants. Different tissues express specific cadherin combinations, which helps cells recognize and stick to the right neighbors.

Cadherins usually bind to the same or a closely related cadherin on another cell. This is called homophilic binding. Because of this matching behavior, cells of the same type tend to group together and form clusters that become tissues.

Cell sorting is important during embryogenesis and development. Early experiments with amphibian embryos showed this clearly. When young embryo cells were separated, mixed, and then allowed to come together again, similar cells clustered and formed structures like the mesoderm, epidermis, and neural tube.

Cadherin expression also changes as cells differentiate. During vertebrate neural tube formation, neural plate cells switch from E-cadherin to N-cadherin as the neural groove forms from the ectoderm. Cells at the neural plate border also begin expressing other cadherins, such as cadherin 6B. These changes help bring the two sides together and support pinching off of the neural tube.

Cadherin-mediated adhesion also helps maintain tissue homeostasis in multicellular organisms. In cancer, this adhesion can break down. Many epithelial tumor cells lose some or all E-cadherin expression, often with help from transcription regulators. One example is Twist, which blocks E-cadherin expression and reduces cell adhesion to neighboring cells.

Cadherins Guide Cell Sorting in Tissues

cell adhesion molecules - types and functions

cell-adhesion-molecules-types-and-functions

Cell Adhesion Molecules in Tissues

Cell adhesion molecules help cells stick together and work as part of a tissue. They give multicellular organisms physical strength and also help cells send signals across the plasma membrane. These proteins are important for coordinated activity in tissues and organ systems. CAMs are grouped into four main families: integrins, cadherins, selectins, and immunoglobulin-like CAMs, or IgCAMs. Each family supports cell interactions in a different way. Some CAMs help cells attach firmly, while...

structure of cadherins

Cadherins in Cell Junctions and Disease

Cadherins are cell adhesion proteins that help cells stick together and build tissues. Their name comes from their calcium-dependent binding. Early examples were named E-cadherin, P-cadherin, and N-cadherin after the epithelial, placental, and neuronal cells where they were first found. Classical cadherins share similar sequences and structures. Other cadherins, including those involved in cell signaling, are grouped as non-classical cadherins. This diversity comes from multiple cadherin genes...

cadherins in tissue organization

Cadherins help cells sort into the right tissues during development. They are a large superfamily of cell adhesion molecules, with more than 180 variants. Different tissues express specific cadherin combinations, which helps cells recognize and stick to the right neighbors. Cadherins usually bind to the same or a closely related cadherin on another cell. This is called homophilic binding. Because of this matching behavior, cells of the same type tend to group together and form clusters that...

catenins

Catenins in Cell Junctions and Signaling

Catenins help cells stay connected and also support signaling inside the body. These proteins act as linker proteins in cell junction complexes because they have multiple binding domains and flexible structures. Most catenins contain a protein sequence called the armadillo repeat, so they are also known as armadillo proteins. Alpha-catenin is the main exception. Catenins bind to cell adhesion molecules such as cadherins. They then connect cadherins to cytoskeletal proteins, and the exact link...

selectins

Selectins in Immune Cell Capture

Selectins help cells make short, temporary contacts during immune responses. They are cell adhesion molecules that bind carbohydrate ligands on other cells. These rod-like proteins have a long outside region and end in a lectin domain, which binds carbohydrates only when calcium ions are present. Three main selectins are known: L-selectin, P-selectin, and E-selectin. Their names reflect where they are found and how long they are. This tissue specificity helps explain why selectins act in...

immunoglobulin-like cell adhesion molecules

immunoglobulin-like-cell-adhesion-molecules

Ig-CAMs in Neural Growth and Disease

Ig-CAMs, or immunoglobulin-like cell adhesion molecules, are cell surface glycoproteins in the immunoglobulin superfamily. They contain immunoglobulin domains, and some also have fibronectin type III domains. Their Ig domains can be glycosylated to different degrees. These molecules can bind to the same kind of Ig-CAM or to other ligands, such as integrins. Most Ig-CAMs help cells stick together only for a short time. The nectin class is different because it helps form stable junctions,...

overview of cell-cell junctions

Cell Junctions in Tissues

Cell junctions help hold tissues together and let neighboring cells communicate. In multicellular organisms, the three-dimensional shape of tissues depends on interactions between cells and the extracellular matrix. Cell-cell junctions are specialized structures made of multi-protein complexes on one cell that connect with similar complexes on another cell. These junctions are grouped into three main types based on function: occluding, anchoring, and gap junctions. Tight junctions, also called...

adherens junctions

Cell Adhesion in Tissues and Infection

Adherens junctions are strong cell-to-cell anchors that help tissues stay connected. These anchoring junctions work with desmosomes, another type of junction that holds adjacent cells together. In many epithelial and endothelial tissues, adherens junctions form a continuous adhesion belt. In heart muscle, they often appear as clusters that help cells work together for coordinated contraction. Adherens junctions are also dynamic, especially in the cells that line blood vessels. These...

tension response at adherens junctions

How Adherens Junctions Sense Force

Adherens junctions help cells stay attached while they respond to mechanical force. These multi-protein complexes can adapt to tensile force and shear stress. When the force changes, mechanosensory proteins in the junction can change shape. This process is called mechanotransduction. Alpha-catenin is one of the main force-sensing proteins in adherens junctions. It is an allosteric protein, which means its shape affects how it works. Alpha-catenin has three VH, or vinculin homology, domains...

desmosomes

Desmosomes and Cell Anchoring

Desmosomes are cell junctions that anchor cells together. They are button-like structures that create an interlinked network of intermediate filaments across cells. This strong link helps tissues resist mechanical stress and maintain tissue integrity. Desmosomes are built from multiple proteins. Their core includes desmosomal cadherins, which are adhesion proteins that bind to cadherins on neighboring cells. The two desmosomal cadherins are desmogleins and desmocollins. These transmembrane...

tight junctions

Tight Junction Proteins and Cell Barriers

Tight junction proteins form seals between neighboring cells. These molecular barriers help stop fluids, ions, and other small solutes from leaking across body cavities and tissue compartments in multicellular organisms. They are an important part of cell barriers in places where controlled movement matters. The main tight junction proteins are claudin and occludin. Other proteins include tricellulin and JAM, which stands for junctional adhesion molecule. Most of these proteins are 4-pass...

gap junctions

Cell Communication Through Gap Junctions

Gap junctions let adjacent animal cells share small molecules, ions, and secondary messengers. These communication channels connect the cytoplasm of neighboring cells. They are built from many molecular channels, often from a few hundred to thousands in one junction. Each channel is made of two halves called connexon hemichannels. A connexon is a hexamer, meaning it is formed by six transmembrane connexin proteins. The six proteins arrange in a ring and create a pore in the center. One...

key terms and concepts

Learn how cadherins help cells stick together, sort into tissues, shape the neural tube, and change during cancer-related EMT in high school biology.

Cadherins Guide Cell Sorting in Tissues | JoVE K12

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Cadherins Guide Cell Sorting in Tissues

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