Name: selectins in immune cell capture
Uploaded: 2023-04-30T11:56:02.000Z
Duration: 1 min 25 s
Channel: JoVE

Селектины представляют собой гликопротеины клеточной поверхности, которые связывают углеводные лиганды и участвуют в транзиторной межклеточной адгезии.
Все селектины содержат N-концевой лектиновый домен и эпидермальный фактор роста или домен EGF, которые регулируют специфичность и силу связывания.
Тем не менее, количество последовательно-консервативных повторов или SCR-доменов может варьироваться от двух до девяти повторов в зависимости от типа селектина.
Короткие L-селектины, экспрессируемые на иммунных клетках, таких как лимфоциты, помогают им мигрировать в лимфатические узлы, связывая лиганды на эндотелиальных клетках.
Более крупные P-селектины в основном экспрессируются на тромбоцитах. Они помогают агрегировать тромбоциты и иммунные клетки в месте повреждения.
Третий тип, называемый Е-селектинами, временно экспрессируется вместе с Р-селектинами на эндотелиальных клетках во время иммунного ответа.
Эти селектины образуют слабые, переходные взаимодействия со свободно текущими лейкоцитами и замедляют их.
Затем лейкоциты катятся по поверхности эндотелия, где другие молекулы клеточной адгезии помогают привлечь их к соответствующему тканевому микроокружению — процесс, называемый хоумингом лейкоцитов.

<ol>
	<li>Борсиг, Любор. "Селектины в иммунитете к раку." Гликобиология 28.9 (2018): 648-655.</li>
	<li>Подагра, Стефани, Пьер-Люк Трембле и Жак Юо. "Селектины и селектиновые лиганды в экстравазации раковых клеток и органной селективности метастазирования." Клинические и экспериментальные метастазы 25.4 (2008): 335-344.</li>
</ol>

Селектины

Selectins

Клеточная адгезия является важным аспектом многоклеточности. В то время как стабильные клеточные взаимодействия обычно происходят между клетками одного и того же типа, временные клеточные взаимодействия происходят между клетками разных типов тканей, например, между нейтрофилами и эндотелиальными клетками. Селектины представляют собой один класс молекул клеточной адгезии (САМ), которые связывают углеводные лиганды с образованием временной клеточной адгезии. Они представляют собой палочковидные белки с длинной внеклеточной частью переменной длины, заканчивающейся лектиновым доменом, который представляет собой лектин С-типа, связывающий углеводы только в присутствии ионов кальция. В зависимости от их тканевой специфичности и длины идентифицируются три основных типа селектинов: L-селектины, P-селектины и E-селектины. Селектины в иммунном ответе Эндотелиальные клетки, выстилающие кровеносные сосуды, экспрессируют P-селектины и хранят их в везикулярных тельцах, называемых тельцами Вейбла-Палада. Во время воспаления стимуляция гистамином быстро мобилизует эти пузырьки на поверхность клетки. Эти активированные эндотелиальные клетки также активируют свои гены E-селектина и P-селектина, тем самым стимулируя их рекрутировать свободно текущие лейкоциты из кровотока. Лейкоциты, такие как нейтрофилы и эозинофилы, экспрессируют углеводные лиганды, такие как PSGL-1, на своей клеточной поверхности. Длинные селектины, выступающие из эндотелиальных клеток, могут легко взаимодействовать с этими лигандами и «подхватывать» свободнотекущие лейкоциты из кровотока. Селектины изначально находятся в закрытой конформации и поэтому слабо связываются со своими лигандами. Однако, по мере движения лейкоцитов напряжение сдвига, возникающее в результате этих взаимодействий, заставляет селектины открываться. Селектины в открытой конформации могут прочно связываться со своими лигандами и, таким образом, способствовать замедлению роста лейкоцитов. Селектины при раке Метастатические раковые клетки нарушают нормальный процесс рекрутирования, опосредованный селекином, и проникают в здоровые ткани. Эти метастатические клетки экспрессируют углеводные лиганды на своей клеточной поверхности и, таким образом, становятся восприимчивыми к связыванию эндотелиальных клеток. При связывании раковые клетки могут покинуть кровеносный сосуд посредством процесса, называемого экстравазацией. Раковые клетки могут затем проникнуть в новое место, вызывая вторичные опухоли.

Клеточная адгезия является важным аспектом многоклеточности. В то время как стабильные клеточные взаимодействия обычно происходят между клетками одного типа, транзиторные ...

Education

JoVE Core

Cell Biology

Клеточная биология

Unit 1

Раздел 1

Cell-Cell Interactions

Межклеточные взаимодействия

KEY TERMS AND CONCEPTS

ОСНОВНЫЕ ТЕРМИНЫ И ПОНЯТИЯ

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 certain cell interactions instead of making permanent attachments.

In blood vessels, endothelial cells line the vessel wall and use selectins to recruit leukocytes during inflammation. These cells store P-selectin in vesicular bodies called Weibel-Palade bodies. When histamine stimulates the cells, the vesicles move quickly to the cell surface. The activated endothelial cells also increase E-selectin and P-selectin gene expression, which prepares them to attract free-flowing leukocytes.

Leukocytes such as neutrophils and eosinophils carry carbohydrate ligands on their surface, including PSGL-1. Long selectins on endothelial cells can reach out and catch these moving cells from the bloodstream. Selectins start in a closed form, so they bind weakly at first. As the leukocyte keeps moving, shear stress from the interaction opens the selectin. In the open form, the selectin binds more strongly and slows the leukocyte down.

Cancer cells can also use this same pathway. Metastatic cancer cells display carbohydrate ligands on their surface and can bind endothelial cells. This lets them leave the blood vessel by extravasation and enter a new tissue. Once there, they can grow into secondary tumors.

Selectins in Immune Cell Capture

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

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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 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

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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 selectins help leukocytes slow down, how inflammation activates endothelial cells, and how metastatic cancer cells use the same pathway.

Selectins in Immune Cell Capture | 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.

Selectins in Immune Cell Capture

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