Feature, Structure and Classifi cation of Adhesion Molecules: An Overview - Adhesion Molecules - page 10

Although integrins bind their ligands with high ai nity following inside-out
activation, stable binding requires their cytoplasmic domains to be anchored to
the cytoskeleton. Integrin-ligand binding triggers integrins to cluster on the cell
surface and leads to the recruitment of enzymes and adaptor molecules that form
adhesion complexes linking integrins to the cytoskeleton (Arnaout et al. 2007).
CADHERINS
h e cadherin superfamily mediates Ca 2+ -dependent cell-cell adhesion. Cadherins
play critical roles in tissue organization and morphogenesis, involving cell
recognition and sorting, coordinated cell movement and the formation and
maintenance of cell and tissue patterning (Ivanov et al. 2001). Cadherins are
dei ned by the presence of cadherin repeats in their extracellular domains. More
than 100 cadherins have been identii ed and are classii ed into subgroups: classical
type I cadherins, type II cadherins, desmosomal cadherins, protocadherins, and
other cadherin-related molecules (Ivanov et al. 2001, Morishita and Yagi 2007).
Basic Structure
Most cadherins comprise an N-terminal extracellular domain containing i ve or
six cadherin repeats, a short transmembrane region and a C-terminal intracellular
domain (Ivanov et al. 2001). h e cadherin repeat unit is about 110 amino acids
and consists of seven strands arranged in a compact β-barrel structure similar to
the Ig-like repeat ( Fig. 5C ) (Van Roy and Berx 2008). h ese repeats are linked by
highly conserved Ca 2+ -binding motifs that provide stability to the extracellular
domain (Ivanov et al. 2001). h e cadherin domains are numbered, with the repeat
closest to the N-terminus designated extracellular cadherin (EC) 1 ( Fig. 5 ) . h e
C-terminal intracellular domain binds to a variety of molecules that link cadherins
to the cytoskeleton.
Cadherin Subgroups
Classical (Type I) Cadherins
h e classical cadherins were the i rst to be described and are named at er the tissue
in which they were identii ed. h e extracellular domain of classical cadherins
consists of an N-terminal pre-domain followed by i ve EC domains, with EC5
characterized by four conserved cysteines not present in the other repeats (Patel
et al. 2003). EC1 contains a conserved tryptophan at position two of the mature
protein (W2) and a hydrophobic pocket capable of accommodating the W2 of a
neighboring EC1 ( Fig. 5C ).