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

Cadherins는 칼슘 의존성 세포 접착 분자 또는 CAM의 superfamily입니다.
모든 cadherins는 작은 C-말단 세포질 도메인, 단일 막관통 도메인 및 여러 세포외 cadherin 또는 EC 도메인으로 구성된 기본 구조를 가지고 있습니다.
이러한 EC 도메인은 각각 3개의 칼슘 결합 포켓이 있는 유연한 힌지 영역으로 서로 연결되어 있습니다.
칼슘 이온이 결합하면 cadherin이 단단해져서 다른 cadherin에 대한 cis- 및 trans-binding이 가능합니다.
시스 결합(cis-binding)에서 동일한 세포의 카드헤린(cadherin)은 서로 결합하여 클러스터를 형성할 수 있으며, 인접 세포에서 카드헤린의 EC 도메인(EC domain)의 상호 작용은 트랜스 결합(trans-binding)을 초래합니다.
막에서 가장 멀리 떨어진 EC1이라고 하는 N-말단 EC 도메인은 손잡이와 포켓 구조를 가지고 있습니다. 트랜스 바인딩하는 동안 한 EC1의 손잡이가 인접한 셀에 있는 다른 EC1의 주머니에 맞습니다.
이것은 한 유형의 cadherins가 동일한 유형의 cadherins를 우선적으로 결합하게 하며, 이는 동성애자 결합입니다.
단일 쌍의 cadherins 사이의 상호 작용은 상대적으로 약하지만, cadherin 클러스터는 집합적으로 강한 trans-binding을 형성할 수 있습니다. 이러한 복합체는 고정 세포 접합을 형성합니다.

<ol>
	<li>Shapiro, Lawrence 및 William I. Weis. "cadherins와 catenins의 구조 및 생화학." Cold Spring Harbor perspectives in biology 1.3 (2009): a003053.</li>
</ol>

카드헤린의 구조

Structure of Cadherins

카드헤린은 발견된 최초의 세포 접착 분자 중 하나였습니다. "카드헤린"이라는 용어는 칼슘 의존성 부착 특성에 기초합니다. 상피 세포, 신경 세포 및 태반 세포에서 발견된 최초의 카드헤린은 각각 E-카드헤린, P-카드헤린 및 N-카드헤린으로 명명되었습니다. 이러한 고전적인 카드헤린은 서열과 구조적 유사성을 공유합니다. 세포 신호 전달에 관여하는 것을 포함한 다른 카드헤린은 비고전적 카드헤린으로 분류됩니다. 이러한 카드헤린의 다양성은 게놈의 여러 카드헤린 유전자와 전사 중 대체 RNA 접합으로 인해 발생합니다.

세포 접합의 카드헤린

카드헤린은 여러 세포외 결합 도메인을 가진 막횡단 단백질입니다. 이의 세포질 도메인은 세포골격에 연결되는 링커 단백질과 결합합니다. 카드헤린은 시스 결합에 의해 원형질막에 함께 모여 세포 접합이라고 불리는 큰 다중 단백질 복합체를 형성합니다. E-카드헤린과 같은 고전적 카드헤린은 부착 접합을 형성하는 반면, 데스모글레인 및 데스모콜린과 같은 비고전적 카드헤린은 부착반점 접합을 형성합니다. 이러한 세포 접합은 세포를 함께 유지하고 상피와 같은 조직에 기계적 강도를 제공하는 기능을 합니다.

카드헤린의 임상적 의의

카드헤린은 세포 부착, 조직 형성 및 세포간 의사소통에 필수적인 역할을 합니다. 결과적으로, 구조, 발현 및 안정성의 변화가 임상 상태로 나타날 수 있습니다. 세포가 이웃 세포와의 접촉을 잃으면 조직에서 벗어나 다른 조직을 침범할 수 있습니다. 카드헤린 유전자의 돌연변이로 인한 세포 부착의 상실은 유방 악성 세포에서 나타나는 것과 같은 종양의 악성 종양과 관련이 있습니다. 병원체는 또한 카드헤린을 수용체로 사용하여 숙주 세포에 부착하고 침입합니다. 예를 들어, 카드헤린 CDHR3은 폐 상피에서 고도로 발현되며 감기를 유발하는 C군 라이노바이러스(RV-C)에 의해 수용체로 사용됩니다.

cadherins는 발견된 첫번째 세포 접착 분자의 한개이었다; "cadherins"라는 용어는 칼슘 의존성을 기반으로 합니다.

Education

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JoVE Core

Cell Biology

세포생물학

Unit 1

제1단원

Cell-Cell Interactions

세포 간 상호작용

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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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