Bouaouina, M., Jani, K., Long, J.Y., Czerniecki, S., Morse, E.M., Ellis, S.J., Tanentzapf, G., Schöck, F., Calderwood, D.A. (2012). Zasp regulates integrin activation.  J. Cell Sci. 125(23): 5647--5657.

FBrf0220880

Research paper

Integrins are heterodimeric adhesion receptors that link the extracellular matrix (ECM) to the cytoskeleton. Binding of the scaffold protein, talin, to the cytoplasmic tail of β-integrin causes a conformational change of the extracellular domains of the integrin heterodimer, thus allowing high-affinity binding of ECM ligands. This essential process is called integrin activation. Here we report that the Z-band alternatively spliced PDZ-motif-containing protein (Zasp) cooperates with talin to activate α5β1 integrins in mammalian tissue culture and αPS2βPS integrins in Drosophila. Zasp is a PDZ-LIM-domain-containing protein mutated in human cardiomyopathies previously thought to function primarily in assembly and maintenance of the muscle contractile machinery. Notably, Zasp is the first protein shown to co-activate α5β1 integrins with talin and appears to do so in a manner distinct from known αIIbβ3 integrin co-activators.

PMC3575701 (PMC) (EuropePMC)