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

신장 및 내장과 같은 기관에서 상피 세포는 거대분자, 이온 및 작은 용질이 세포 주위 공간을 통해 흐르는 것을 방지하기 위해 단단한 접합부로 함께 밀봉되어 있습니다.
밀접연연은 주로 claudin 및 occludin 막관통 단백질로 구성되며, 각 단백질에는 4개의 막에 걸쳐 있는 알파 나선이 있습니다.
claudins와 occludins의 행은 멤브레인에서 중합되어 밀봉 가닥의 네트워크를 형성합니다.
이 가닥은 세포 외 고리에 의해 인접한 세포의 유사한 단백질 가닥에 부착되어 두 개의 막을 함께 고정합니다.
세포질 쪽에서 이러한 단백질의 C 말단 꼬리는 zonula occludens 또는 ZO라고 하는 큰 골격 단백질의 PDZ 도메인과 연결됩니다.
ZO 단백질은 여러 단백질 결합 도메인을 가지고 있으므로 클라우딘, 오클루딘, 액틴 및 기타 ZO 단백질과 결합하여 이러한 밀봉 가닥을 구성하고 안정화하는 그물망을 형성할 수 있습니다.
세포주위 공간을 밀봉하는 것 외에도, 밀접연접은 포도당 수송체(glucose transporter)와 같은 단백질이 세포막을 따라 측면으로 이동하는 것을 방지합니다. 이것은 포도당 흡수를 위해 이러한 단백질을 장 상피의 정점 표면에 국한시키는 데 도움이 됩니다.

<ol>
	<li>사와다, 典正. "밀접 접합 관련 인간 질환." 국제 병리학 63.1 (2013) : 1-12. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168075/">링크</a></li>
	<li>앤더슨, 제임스 M., 크리스티나 M. 밴 이탈리. "밀착 접합의 생리학과 기능." 생물학의 콜드 스프링 하버 관점 1.2 (2009): a002584. <a href="https://cshperspectives.cshlp.org/content/1/2/a002584.full">링크</a></li>
	<li>Mariano, Cibelle, et al. "타이트 접합 형성 및 유지에서 트리셀룰린과 그 역할에 대한 고찰." 세포 생물학의 유럽 저널 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">링크</a></li>
</ol>

밀착연접

Tight Junctions

밀착연접은 다세포 유기체의 공동과 구획을 통해 체액, 이온 및 기타 작은 용질이 누출되는 것을 방지하는 세포 간의 분자 봉인입니다. 이는 주로 클라우딘 및 오클루딘 연결단백질과 트리셀룰린 및 JAM(junctional attachment Molecule)과 같은 기타 단백질로 구성됩니다. 면역글로불린 슈퍼패밀리에 속하는 단일 통과 막횡단 단백질인 JAM을 제외한 모든 단백질은 4-패스 막횡단 단백질입니다. 이러한 밀착연접 단백질의 세포외 도메인은 인접한 세포막의 도메인과 상호작용하여 인접한 두 세포를 하나로 모으고 밀봉합니다.

밀착연접의 선택적 투자율

막관통 클라우딘에는 다양한 동형이 있으며, 최대 24가지 유형이 인간에서 발현됩니다. 클라우딘 단백질의 다양성은 다양한 밀착연접에 선택적 투과성을 부여합니다. 예를 들어, 신장 상피에서 발현되는 클라우딘-16은 마그네슘 이온에 대한 투과성을 증가시켜 여과 중에 혈액에서 재흡수되도록 합니다. 대조적으로, 뇌 모세혈관의 내피 세포에서 발현되는 클라우딘-5는 혈액-뇌 장벽을 통한 이온 투과성을 선택적으로 감소시킵니다.

삼세포연접

두 세포 사이의 간격을 밀봉하는 것 외에도, 밀착연접은 세 세포의 연접부(삼세포연접)에 형성된 틈도 밀봉합니다. 삼세포연접의 구조는 1970년대 동결-파괴 전자현미경을 사용하여 처음으로 관찰되었습니다. 이러한 연접부에서 밀봉 가닥은 이중 세포 밀착연접의 가닥에 수직으로 배향됩니다. 따라서 삼세포 접촉점은 분자의 세포간 이동을 제어하는 약 10nm 직경의 좁은 수직 튜브를 형성합니다.

트리셀룰린은 이러한 삼세포 연접부에 집중되어 있는 것으로 확인된 최초의 단백질이었습니다. 이는 오클루딘 단백질과 서열 상동성을 공유하며 인간에서 4개의 이소형을 나타냅니다. 흥미롭게도 트리셀룰린 유전자인 TRIC의 돌연변이는 청력 손상을 일으키는 것으로 나타났으며, 이는 내이의 구조인 코르티 기관에 필요한 것과 같은 긴밀한 밀봉을 유지하는 데 있어 중요성을 입증합니다.

Tight junctions는 세포 사이의 분자 밀봉으로, 유체, 이온 및 기타 작은 용질이 공동과 구획을 가로질러 누출되는 것을 방지합니다.

Education

교육

JoVE Core

Cell Biology

세포생물학

Unit 1

제1단원

Cell-Cell Interactions

세포 간 상호작용

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 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.

Tight Junction Proteins and Cell Barriers

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