Cell adhesion molecules ( CAMs ) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion . In essence, CAMs help cells stick to each other and to their surroundings. CAMs are crucial components in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in generating force and movement and consequently ensuring that organs are able to execute their functions normally. In addition to serving as "molecular glue", CAMs play important roles in the cellular mechanisms of growth, contact inhibition, and apoptosis. Aberrant expression of CAMs may result in a wide range of pathologies, ranging from frostbite to cancer.
21-691: 1CDB , 1GYA , 1HNF , 1L2Z , 1QA9 , 2J6O , 2J7I 914 12481 ENSG00000116824 ENSMUSG00000027863 P06729 Q53F96 P08920 NM_001767 NM_001328609 NM_013486 NP_001315538 NP_001758 NP_001758.2 NP_038514 CD2 (cluster of differentiation 2) is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells . It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor. It interacts with other adhesion molecules, such as lymphocyte function-associated antigen-3 (LFA-3/ CD58 ) in humans, or CD48 in rodents, which are expressed on
42-517: A characteristic Ig-fold , which has a sandwich-like structure formed by two sheets of antiparallel beta strands . Interactions between hydrophobic amino acids on the inner side of the sandwich and highly conserved disulfide bonds formed between cysteine residues in the B and F strands, stabilize the Ig-fold. The Ig like domains can be classified as IgV, IgC1, IgC2, or IgI. Most Ig domains are either variable (IgV) or constant (IgC). The Ig domain
63-438: A crucial role in orchestrating circulating lymphocytes. CAM function in cancer metastasis, inflammation, and thrombosis makes it a viable therapeutic target that is currently being considered. For example, they block the metastatic cancer cells' ability to extravasate and home to secondary sites. This has been successfully demonstrated in metastatic melanoma that hones to the lungs. In mice, when antibodies directed against CAMs in
84-459: A domain known as an immunoglobulin domain or fold . Members of the IgSF include cell surface antigen receptors, co-receptors and co-stimulatory molecules of the immune system , molecules involved in antigen presentation to lymphocytes , cell adhesion molecules , certain cytokine receptors and intracellular muscle proteins. They are commonly associated with roles in the immune system. Otherwise,
105-422: Is regarded as the most diverse superfamily of CAMs. This family is characterized by their extracellular domains containing Ig-like domains. The Ig domains are then followed by Fibronectin type III domain repeats and IgSFs are anchored to the membrane by a GPI moiety. This family is involved in both homophilic or heterophilic binding and has the ability to bind integrins or different IgSF CAMs. Integrins , one of
126-495: The cytoskeleton , a transmembrane domain, and an extracellular domain. These proteins can interact in several different ways. The first method is through homophilic binding, where CAMs bind with the same CAMs. They are also capable of heterophilic binding, meaning a CAM on one cell will bind with different CAMs on another cell. There are four major superfamilies or groups of CAMs: the immunoglobulin super family of cell adhesion molecules ( IgCAMs ), Cadherins , Integrins , and
147-564: The CAMS that are particularly important in the lymphocyte homing is addressin . Lymphocyte homing is a key process occurring in a strong immune system. It controls the process of circulating lymphocytes adhering to particular regions and organs of the body. The process is highly regulated by cell adhesion molecules, particularly, the addressin also known as MADCAM1. This antigen is known for its role in tissue-specific adhesion of lymphocytes to high endothelium venules. Through these interactions they play
168-449: The ECDs are necessary for cell adhesion . The cytoplasmic domain has specific regions where catenin proteins bind. The selectins are a family of heterophilic CAMs that are dependent on fucosylated carbohydrates, e.g., mucins for binding. The three family members are E-selectin ( endothelial ), L-selectin ( leukocyte ), and P-selectin ( platelet ). The best-characterized ligand for
189-576: The Superfamily of C-type of lectin-like domains proteins ( CTLDs ). Proteoglycans are also considered to be a class of CAMs. One classification system involves the distinction between calcium-independent CAMs and calcium-dependent CAMs. The Ig-superfamily CAMs do not depend on Ca while integrins, cadherins and selectins depend on Ca . In addition, integrins participate in cell–matrix interactions, while other CAM families participate in cell–cell interactions. Immunoglobulin superfamily CAMs (IgSF CAMs)
210-453: The alpha and beta subunits there is a large extracellular domain, a transmembrane domain and a short cytoplasmic domain. The extracellular domain is where the ligand binds through the use of divalent cations . The integrins contain multiple divalent cation binding sites in the extracellular domain ). The integrin cation binding sites can be occupied by Ca2+ or by Mn2+ ions. Cations are necessary but not sufficient for integrins to convert from
231-839: The formation of the mesoderm , endoderm , and ectoderm . Cadherins also contribute significantly to the development of the nervous system. The distinct temporal and spatial localization of cadherins implicates these molecules as major players in the process of synaptic stabilization . Each cadherin exhibits a unique pattern of tissue distribution that is carefully controlled by calcium. The diverse family of cadherins include epithelial (E-cadherins), placental (P-cadherins), neural (N-cadherins), retinal ( R-cadherins ), brain (B-cadherins and T-cadherins), and muscle (M-cadherins). Many cell types express combinations of cadherin types. The extracellular domain has major repeats called extracellular cadherin domains (ECD). Sequences involved in Ca binding between
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#1732859061758252-553: The inactive bent conformation into the active extended conformation. Both the presence of cations bound to the multiple cation binding sites is required, along with the direct physical association with ECM ligands for integrins to attain the extended structure and concomitant activation. Thus, rise in extracellular Ca2+ ions may serve to prime the integrin heterodimer. The release of intracellular Ca2+ have been shown to be important for integrin inside-out activation. However, extracellular Ca2+ binding may exert different effects depending on
273-498: The integrin into its high affinity state, which causes increased fibrinogen binding, causing platelet aggregation. The cadherins are homophilic Ca -dependent glycoproteins . The classic cadherins ( E- , N- and P- ) are concentrated at the intermediate cell junctions , which link to the actin filament network through specific linking proteins called catenins . Cadherins are notable in embryonic development. For example, cadherins are crucial in gastrulation for
294-513: The lung endothelium were used as treatment there was a significant reduction in the number of metastatic sites. Immunoglobulin superfamily The immunoglobulin superfamily ( IgSF ) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells . Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins (also known as antibodies); they all possess
315-636: The major classes of receptors within the ECM, mediate cell–ECM interactions with collagen , fibrinogen , fibronectin , and vitronectin . Integrins provide essential links between the extracellular environment and the intracellular signalling pathways, which can play roles in cell behaviours such as apoptosis , differentiation , survival , and transcription . Integrins are heterodimeric , as they consist of an alpha and beta subunit. There are currently 18 alpha subunits and 8 beta subunits, which combine to make up 24 different integrin combinations. Within each of
336-510: The presence of the antigen to distinguish these conditions from B cell neoplasms . Due to its structural characteristics, CD2 is a member of the immunoglobulin superfamily ; it possesses two immunoglobulin-like domains in its extracellular portion. CD2 has been shown to interact with CD2BP2 , Lck and PSTPIP1 . Cell adhesion molecule CAMs are typically single-pass transmembrane receptors and are composed of three conserved domains: an intracellular domain that interacts with
357-493: The sperm-specific protein IZUMO1 , a member of the immunoglobulin superfamily, has also been identified as the only sperm membrane protein essential for sperm-egg fusion. Proteins of the IgSF possess a structural domain known as an immunoglobulin (Ig) domain . Ig domains are named after the immunoglobulin molecules. They contain about 70-110 amino acids and are categorized according to their size and function. Ig-domains possess
378-400: The surfaces of other cells. In addition to its adhesive properties, CD2 also acts as a co-stimulatory molecule on T and NK cells. CD2 is a specific marker for T cells and NK cells, and can therefore be used in immunohistochemistry to identify the presence of such cells in tissue sections. The great majority of T cell lymphomas and leukaemias also express CD2, making it possible to use
399-446: The three selectins is P-selectin glycoprotein ligand-1 ( PSGL-1 ), which is a mucin-type glycoprotein expressed on all white blood cells. Selectins have been implicated in several roles but they are especially important in the immune system by helping white blood cell homing and trafficking. The variety in CAMs leads to diverse functionality of these proteins in the biological setting. One of
420-432: The type of integrin and the cation concentration. Integrins regulate their activity within the body by changing conformation. Most exist at rest in a low affinity state, which can be altered to high affinity through an external agonist which causes a conformational change within the integrin, increasing their affinity. An example of this is the aggregation of platelets ; Agonists such as thrombin or collagen trigger
441-416: Was reported to be the most populous family of proteins in the human genome with 765 members identified. Members of the family can be found even in the bodies of animals with a simple physiological structure such as poriferan sponges. They have also been found in bacteria, where their presence is likely to be due to divergence from a shared ancestor of eukaryotic immunoglobulin superfamily domains. Similar to
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