The cell. 3. Cell membrane.
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Cells adhere to neighbour structures by transmembrane proteins located in the plasma membrane.
Cell-extracellular matrix adhesion is the adhesion of the cell to the extracellular matrix mainly mediated by integrins.
Cell-cell adhesion is the adhesion between adjoining cells mainly mediated by cadherins, immunoglobulins, selectins and integrins.
Adhesion has more functions than only the cellular mechanical support but it is also a transduction mechanism to let know to the cell about the extracellular environment, which produces cellular behavioural changes and may lead to gene expression.
Cell-extracellular matrix adhesion.
Integrins are probably the most important proteins involved in the adhesion between cells and extracellular matrix, and comprise a large family of proteins which is present in all animals. Integrins are transmembrane proteins composed of two subunits (alpha and beta). In mammals, integrins family is made up of 18 alpha units and 3 beta units, that when combined are able to form up to 24 different integrins, which are differentially expressed depending on the tissue and physiological state of the cell. Integrins have 3 molecular domains. One intracellular domain which interplays with actin cytoskeleton filaments, one extracellular domain that can bind collagen, fibronectins and laminins, and one intramembrane domain which is a hydrophobic amino acid sequence inserted among the lipids fatty acid chains. The ability of integrins to connect extracellular matrix and cytoskeleton makes possible a structural continuity between inside and outside of the cell. Furthermore, integrins may change the behavior of the cell according to the molecular composition of the extracellular matrix. This is possible because the adhesion state of integrin is transmitted to the its intracellular domain by conformational change, triggering molecular interaction cascades in the cytosol, that eventually may change gene expression. Cells, in turn, may regulate the strength of adhesion by increasing or decreasing the number of integrins, or by synthesizing different subunit subtypes, or by molecular interaction with the intracellular domain, which in turn will modify the adhesion ability of the extracellular domain.
Integrin, states of activity (Modified from Luo et al., 2007).
Sometimes, integrins are gathered together in groups to form macromolecular complexes known as focal adhesions and hemidesmosomes.
Main adhesion molecules making cell-cell contacts (modified from Hynes, 1999).
There are transmembrane molecules that make direct adhesion contacts between cells. There are four types: cadherins, immunoglobulins, selectins and some types of integrins. Cadherins are found in most of the animal cells and make homotypic contacts, i.e. they recognize and join other cadherins located in neighbour cells. Cadherins are a large family of proteins, with some members specifically expressed in some tissues. For example, N-cadherins are found in the nervous tissue, and E-cadherin in epithelial tissue. This is why they play an important role during segregation of cell populations in tissues during development, but also in adults. Cadherins are particularly relevant during embryonic development. Cadherins are also found as structural parts of desmosomes (macula adherens) and adherent junctions (zonula adherens). Some adhesion proteins, also known as CAM (cell adhesion molecules), belong to the immunoglobulin family and make homophilic contacts with other immunoglobulins located in neighbour cells, although they are also able to make heterophilic contacts. CAM are a large family of proteins with a specific expression pattern in the body organs and tissues. For example, N-CAM is expressed in the nervous system. The binding strength of CAM proteins is weaker than cadherins, and it is thought that this is suitable to fine tune the segregation of cells in groups inside tissues. Selectins are another type of adhesion molecule involved in cell-cell adhesion by heterophilic contacts. They bind carbohydrates (sialic acid and fucose) located in the surface of the neighbour cells. For example, they are needed during the exit of leukocytes from blood vessels toward the extracellular matrix of surrounding tissues, because they allow the attachment of leukocytes to the endothelial surface. Integrins, which mainly participate in cell-extracellular matrix adhesion, are also involved in cell-cell adhesion. For example, some integrins can make heterophilic contacts with certain types of immunoglobulins of neighbour cells.
Hynes RO. 1999. Cell adhesion: old and new questions. Trends in neurosciences. 9(12): M33-M37.☆
Luo BH, Carman CV, Springer TA. 2007. Structural basis of integrin regulation and signaling. Annual review of immunology. 24: 619-647.☆
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Updated: 28-01-2018. 15:16
Atlas of Plant and Animal Histology
Dep. of Functional Biology and Health Sciences.
Faculty of Biology.
University of Vigo