Overview
Cells in tissues attach to each other and to the extracellular matrix through adhesion molecules, which are linked inside the cell to the cytoskeleton. This topic covers the mechanisms of adhesion, the adhesion molecules (integrins, cadherins and immunoglobulin-like molecules), the cytoskeleton (actin filaments, intermediate filaments, microtubules), the types of cell contacts and the clinical significance of defects.
Mechanisms of cell adhesion and adhesion molecules
Cell adhesion molecules (CAMs) are transmembrane glycoproteins with an extracellular part that binds a ligand and an intracellular part that binds adaptor proteins and the cytoskeleton. They bind homophilically (the same molecule on the neighbouring cell) or heterophilically (a different ligand, for example integrin to matrix protein). Single bonds are weak, so strong adhesion comes from the clustering of many molecules. Adhesion molecules also transmit signals (outside-in and inside-out) that control survival, shape, migration and proliferation.
Cadherins
Cadherins are single-pass transmembrane proteins with five extracellular repeats that bind Ca²⁺; without Ca²⁺ they become floppy and lose adhesion. They bind homophilically, so cells of one type tend to stick together and sort from other cells during development: E-cadherin (epithelia), N-cadherin (nerve, muscle, fibroblasts), P-cadherin (placenta), VE-cadherin (endothelium). The cytoplasmic tail binds catenins (β-catenin, p120, and through α-catenin the actin filaments). Desmosomal cadherins (desmoglein and desmocollin) bind plakoglobin, plakophilin and desmoplakin and are linked to intermediate filaments. β-catenin is also a signalling molecule in the Wnt pathway.
Immunoglobulin-like adhesion molecules
These contain Ig-like domains and do not need Ca²⁺. NCAM binds homophilically in the nervous system. ICAM-1/2 and VCAM-1 on endothelium bind the integrins LFA-1 (αLβ2) and VLA-4 (α4β1) of leukocytes and hold them for transmigration into tissue during inflammation; PECAM-1 assists passage between endothelial cells. Nectins start adherens junctions and JAMs belong to tight junctions.
Selectins
L-, E- and P-selectin bind sialyl-Lewis X on glycoproteins and mediate the first, weak contact with the vessel wall (rolling) of leukocytes. Firm adhesion then follows through integrin activation and binding to ICAMs.