The Role of Tetraspanins in Cell Migration and Intercellular Adhesion

Tetraspanin-enriched microdomains (TEMs) are specialized platforms in the plasma membrane that include certain adhesion receptors, mainly integrins and receptors of the Ig superfamily. Insertion into TEMs increases the local concentration of these adhesion receptors, facilitating their function as avidity regulators. TEMs also regulate interaction and crosstalk between different receptors at the plasma membrane, as well as their internalization rate. Moreover, certain signaling pathways are regulated by association with tetraspanins. Thus, tetraspanins emerge as critical regulators of biological phenomena involving adhesion to the extracellular matrix or homotypic or heterotypic intercellular interactions. These proteins are implicated in different steps of cancer progression, the regulation of intercellular adhesion between polarized epithelial cells, angiogenesis, antigen presentation and extravasation of leukocytes or tumor cells. In addition, several pathogens hijack these tetraspanin-adhesion platforms to increase their infectivity.