Name: cadherins in cell junctions and disease
Uploaded: 2023-04-30T11:54:59.000Z
Duration: 1 min 25 s
Channel: JoVE

Кадгерины представляют собой надсемейство кальций-зависимых молекул клеточной адгезии или CAM.
Все кадгерины имеют базовую структуру, состоящую из небольшого С-концевого цитозольного домена, одного трансмембранного домена и нескольких внеклеточных доменов кадгерина или EC.
Эти EC-домены связаны друг с другом гибкими шарнирными областями, каждая из которых имеет три кальций-связывающих кармана.
Когда ионы кальция связываются, кадгерин становится жестким, что позволяет цис- и транссвязываться с другими кадгеринами.
При цис-связывании кадгерины на одной и той же клетке могут связываться друг с другом, образуя кластеры, в то время как взаимодействие EC-доменов кадгеринов на соседних клетках приводит к транссвязыванию.
N-концевой домен EC, наиболее удаленный от мембраны, называемый EC1, имеет структуру ручки и кармана. Во время перепривязки ручка одного EC1 помещается в карман другого EC1 на соседней клетке.
Это заставляет кадгерины одного типа преимущественно связывать кадгерины того же типа, гомофильного связывания.
Несмотря на то, что взаимодействие между одной парой кадгеринов относительно слабое, кластеры кадгеринов могут образовывать коллективно сильное транссвязывание. Такие комплексы образуют якорные клеточные соединения.

<ol>
	<li>Шапиро, Лоуренс и Уильям И. Вайс. "Структура и биохимия кадгеринов и катенинов." Перспективы Колд-Спринг-Харбор в биологии 1.3 (2009): a003053.</li>
</ol>

Структура кадгеринов

Structure of Cadherins

Кадгерины были одними из первых обнаруженных молекул клеточной адгезии; термин «кадгерины» основан на их кальций-зависимых свойствах прилипания. Первые кадгерины, обнаруженные на эпителиальных, нейрональных и плацентарных клетках, были названы E-кадгерин, P-кадгерин и N-кадгерин соответственно. Эти классические кадгерины имеют общие последовательности и структурные сходства. Другие кадгерины, в том числе участвующие в передаче сигналов в клетках, группируются в неклассические кадгерины. Это разнообразие кадгеринов возникает из-за множества генов кадгеринов в геноме и альтернативного сплайсинга РНК во время транскрипции. Кадгерины в клеточных соединениях Кадгерины представляют собой трансмембранные белки с множеством внеклеточных связывающих доменов. Их цитозольный домен связывает линкерные белки, которые соединяются с цитоскелетом. Кадгерины группируются на плазматической мембране посредством цис-связывания, образуя большие мультибелковые комплексы, называемые клеточными соединениями. В то время как классические кадгерины, такие как E-кадгерин, образуют адгезивные соединения, неклассические кадгерины, такие как десмоглеин и десмоколлин, образуют десмосомальные соединения. Эти клеточные соединения удерживают клетки вместе и обеспечивают механическую прочность тканям, таким как эпителий. Клиническое значение кадгеринов Кадгерины играют важную роль в клеточной адгезии, формировании тканей и межклеточной коммуникации. Следовательно, любые изменения в их структуре, экспрессии и стабильности могут проявляться клиническими состояниями. Когда клетки теряют контакт с соседними клетками, они могут вырваться из ткани и проникнуть в другие ткани. Потеря клеточной адгезии из-за мутаций в генах кадгерина связана со злокачественным новообразованием, например, наблюдаемым в злокачественных клетках молочной железы. Патогены также используют кадгерины в качестве рецепторов для прикрепления и проникновения в клетку-хозяина. Например, кадгерин CDHR3 высоко экспрессируется в эпителии легких и используется в качестве рецептора риновирусом класса C (RV-C), вызывающим простуду.

Кадгерины были одними из первых обнаруженных молекул клеточной адгезии; Термин «кадгерины» основан на их кальций-зависимых...

Education

JoVE Core

Cell Biology

Клеточная биология

Unit 1

Раздел 1

Cell-Cell Interactions

Межклеточные взаимодействия

KEY TERMS AND CONCEPTS

ОСНОВНЫЕ ТЕРМИНЫ И ПОНЯТИЯ

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 in the genome and from alternative RNA splicing during transcription.

Cadherins are transmembrane proteins. They have several extracellular binding domains and a cytosolic domain inside the cell. The cytosolic region binds linker proteins, which connect cadherins to the cytoskeleton. Cadherins also cluster on the plasma membrane through cis-binding, which helps form large protein complexes called cell junctions.

Classical cadherins such as E-cadherin form adherens junctions. Non-classical cadherins such as desmoglein and desmocollin form desmosomal junctions. These junctions hold cells together and give mechanical strength to tissues such as epithelium.

Cadherins are important for cell adhesion, tissue formation, and communication between cells. Changes in their structure, expression, or stability can lead to disease. When cells lose contact with neighboring cells, they may break free from the tissue and invade other tissues. Mutations in cadherin genes are linked to tumor malignancy, including in breast cancer cells. Some pathogens also use cadherins as receptors to attach to and enter host cells. One example is CDHR3, which is highly expressed in lung epithelium and is used by class-C rhinovirus, or RV-C, the virus that causes the common cold.

Cadherins in Cell Junctions and Disease

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 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 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, form junctions, and support tissues, and how changes in cadherins can contribute to cancer and infection.

Cadherins in Cell Junctions and Disease | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Cadherins in Cell Junctions and Disease

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