Name: tight junction proteins and cell barriers
Uploaded: 2023-04-30T11:55:38.000Z
Duration: 1 min 29 s
Channel: JoVE

Em órgãos como rins e intestinos, as células epiteliais são seladas com junções apertadas para impedir o fluxo de macromoléculas, íons e pequenos solutos através do espaço paracelular.
As junções apertadas compreendem principalmente proteínas transmembranares de claudina e oclusina, cada uma com quatro alfa-hélices que atravessam a membrana.
Fileiras de claudinas e oclusinas polimerizam na membrana, formando uma rede de fios de vedação.
Essas fitas se ligam a fitas semelhantes de proteínas na célula adjacente por suas alças extracelulares, mantendo as duas membranas juntas.
No lado citoplasmático, as caudas C-terminais dessas proteínas se associam aos domínios PDZ de grandes proteínas de andaime chamadas zonula occludens ou ZO.
As proteínas ZO têm múltiplos domínios de ligação a proteínas e, portanto, podem se ligar a claudinas, oclusinas, actina e outras proteínas ZO, formando uma malha que organiza e estabiliza essas fitas de vedação.
Além de selar o espaço paracelular, as junções apertadas também impedem o movimento lateral de proteínas, como os transportadores de glicose, ao longo da membrana. Isso ajuda a localizar essas proteínas na superfície apical do epitélio intestinal para absorção de glicose.

<ol>
	<li>Sawada, Norimasa. "Doenças humanas relacionadas à junção apertada." Patologia internacional 63.1 (2013): 1-12. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168075/">Link</a></li>
	<li>Anderson, James M. e Christina M. Van Itallie. "Fisiologia e função da junção apertada." Perspectivas de Cold Spring Harbor em biologia 1.2 (2009): a002584. <a href="https://cshperspectives.cshlp.org/content/1/2/a002584.full">Link</a></li>
	<li>Mariano, Cibelle, et al. "Um olhar sobre a tricelilina e seu papel na formação e manutenção de junções apertadas." Revista Europeia de Biologia Celular 90.10 (2011): 787-796. <a href=" https://d1wqtxts1xzle7.cloudfront.net/52322075/A_look_at_tricellulin_and_its_role_in_ti20170327-17112-1qhpwe8-libre.pdf?1490608194=&response-content-disposition=inline%3B+filename%3DA_look_at_tricellulin_and_its_role_in_ti.pdf&Expires=1654205963&Signature=IelR0FUZCC6ZcqAcJvs1JTGe6liRDBX6aqaYzcw4sMZ2yqyhu5BuZ9DDbujaDRUN9SwX20yuCRLRyzxl6MWAa4QfY2cZ1wtZb4qfoi5otW~z0rhB3ba231uB1~pdP0rZpdHB4~snYhLr-~nZRsoaUqTFJmJaJXpxtHnoBGC4HFP29Q8D3q0rNHNDJGq9Qx9SfcLWmDISH7n8IfsUozT6rdpn421eOVufn5lNVunpqMX6iiRAT4D7p8bJEPpfd2~3cygJP7Ltc32RiIm2RHGvp9CRUoXs015y2aR4A7--dka7UzL97Aa~DDZ8ES90wX9D58qA~jX24DnmzNeNwlAayg__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA ">Link</a></li>
</ol>

junções estreitas

Tight Junctions

As junções Estreitas, ou apertadas, são selos moleculares entre as células que evitam o vazamento de fluidos, íons e outros pequenos solutos através de cavidades e compartimentos em organismos multicelulares. Elas são compostas principalmente pelas proteínas transmembranares claudina e ocludina, e outras proteínas, como tricelulina e JAM (molécula de adesão juncional). Todas essas proteínas são proteínas transmembranares de 4 passagens, exceto a JAM, que é uma proteína transmembrana de passagem única pertencente à superfamília das imunoglobulinas. Os domínios extracelulares destas proteínas de junção estreita interagem com aqueles da membrana celular adjacente, unindo e selando assim as duas células adjacentes. Permeabilidade seletiva das junções estreitas Existem múltiplas isoformas da claudina transmembrana, com até 24 tipos diferentes expressos em humanos. A diversidade da proteína claudina confere permeabilidade seletiva a diferentes junções estreitas. Por exemplo, a claudina-16, expressa no epitélio renal, aumenta a permeabilidade aos íons de magnésio, permitindo assim a sua recaptação do sangue durante a filtração. Em contraste, a claudina-5 expressa nas células endoteliais dos capilares cerebrais diminui seletivamente a permeabilidade iônica através da barreira hematoencefálica. Junções Tricelulares Além de vedar as lacunas entre duas células, as junções estreitas também vedam as lacunas formadas na junção de três células - uma junção tricelular. A estrutura das junções tricelulares foi observada pela primeira vez na década de 1970 usando microscopia eletrônica de fratura por congelamento. Nessas junções, os fios de vedação são orientados perpendicularmente aos fios das junções estreitas bicelulares. O ponto de contato tricelular forma assim um tubo vertical estreito com cerca de 10 nm de diâmetro, que controla o movimento paracelular das moléculas. A tricelulina foi a primeira proteína identificada a concentrar-se nessas junções tricelulares. Ela compartilha homologia de sequência com as proteínas ocludina e exibe quatro isoformas em humanos. Curiosamente, foi demonstrado que mutações no gene da tricelulina, TRIC, causam deficiência auditiva, demonstrando a sua importância na manutenção de vedações herméticas, como as exigidas no órgão de Corti – uma estrutura no ouvido interno.

Junções Estreitas

As junções apertadas são selos moleculares entre as células que impedem o vazamento de fluidos, íons e outros pequenos solutos através de cavidades e compartimentos em ...

Education

JoVE Core

Cell Biology

Biologia Celular

Unit 1

Unidade 1

Cell-Cell Interactions

Interações Célula-Célula

KEY TERMS AND CONCEPTS

TERMOS-CHAVE E CONCEITOS

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 transmembrane proteins, meaning they cross the cell membrane four times. JAM is different because it is a single-pass transmembrane protein in the immunoglobulin superfamily. The extracellular parts of these proteins interact with matching parts on the nearby cell membrane. This brings two adjacent cells together and helps seal them.

Claudin proteins are especially important because there are many isoforms, or forms, of claudin. Humans express up to 24 different types. This diversity gives tight junctions selective permeability, which means some substances pass more easily than others. For example, claudin-16 in kidney epithelium increases permeability to magnesium ions. This helps magnesium move back into the body during filtration. In contrast, claudin-5 in endothelial cells of brain capillaries lowers ion permeability across the blood-brain barrier.

Tight junctions also seal tricellular junctions, which are the gaps where three cells meet. These junctions were first seen in the 1970s with freeze-fracture electron microscopy. At these contact points, the sealing strands run perpendicular to the strands in bicellular tight junctions. The center of the tricellular contact forms a narrow vertical tube about 10 nm wide. This structure helps control paracellular movement, which is movement between cells.

Tricellulin is the first protein known to concentrate at tricellular junctions. It is related in sequence to occludin and has four isoforms in humans. Mutations in the tricellulin gene, TRIC, can cause hearing impairment. This shows how important tight seals are in the organ of Corti, a structure in the inner ear.

Tight Junction Proteins and Cell Barriers

tight-junction-proteins-and-cell-barriers

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 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...

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 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 claudin, occludin, tricellulin, and JAM seal cells, control selective permeability, and support barriers like the blood-brain barrier.

Tight Junction Proteins and Cell Barriers | JoVE K12

cell biology

JoVE Core - Biologia Celular ilustra processos celulares complexos em vídeos de animação fáceis de entender e, ao mesmo tempo, abrangentes. Esta coleção foca nos componentes e funções essenciais das células, incluindo organelas e membranas, transporte celular e energia celular. É complementado por vídeos de Cientistas em ação que demonstram a aplicação da biologia celular em experimentos de pesquisa do mundo real.

Tight Junction Proteins and Cell Barriers

Description

Transcript

Tags