Cell adhesion molecule
Cell adhesion molecules (CAMs) are a subset of cell surface proteins[1] that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion.[2] 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.[3] 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.[4]
Structure
CAMs are typically single-pass
Families of CAMs
There are four major superfamilies or groups of CAMs: the
One classification system involves the distinction between calcium-independent CAMs and calcium-dependent CAMs.[7] The Ig-superfamily CAMs do not depend on Ca2+ while integrins, cadherins and selectins depend on Ca2+. In addition, integrins participate in cell–matrix interactions, while other CAM families participate in cell–cell interactions.[8]
Calcium-independent
IgSF CAMs
Immunoglobulin superfamily CAMs (IgSF CAMs) 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.[citation needed]
Calcium-dependent
Integrins
Integrins are
An example of this is the aggregation of
Cadherins
The
Cadherins are notable in embryonic development. For example, cadherins are crucial in gastrulation for 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).[18] Many cell types express combinations of cadherin types.
The
binding between the ECDs are necessary for cell adhesion. The cytoplasmic domain has specific regions where catenin proteins bind.[19]
Selectins
The
Biological function of CAMs
The variety in CAMs leads to diverse functionality of these proteins in the biological setting. One of the CAMS that are particularly important in the lymphocyte homing is addressin.[21] 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.[22] 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.[23] Through these interactions they play 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 the lung endothelium were used as treatment there was a significant reduction in the number of metastatic sites.[24]
See also
References
- ^ Cell+Adhesion+Molecules at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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- ^ "Single-pass transmembrane adhesion and structural proteins". membranome. College of Pharmacy, University of Michigan. Retrieved October 20, 2018.in Membranome database
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- ^ Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James (2000-01-01). "Cell–Cell Adhesion and Communication".
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- ^ a b c Schnapp, L (2006). Integrin, Adhesion/cell-matrix. Seattle: Elsevier.
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