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Zasp regulates integrin activation.

ABSTRACT: 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 ?-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 ?5?1 integrins in mammalian tissue culture and ?PS2?PS 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 ?5?1 integrins with talin and appears to do so in a manner distinct from known ?IIb?3 integrin co-activators.

SUBMITTER: Bouaouina M

PROVIDER: S-EPMC3575701 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Zasp regulates integrin activation.

Bouaouina Mohamed M Jani Klodiana K Long Jenny Y JY Czerniecki Stefan S Morse Elizabeth M EM Ellis Stephanie J SJ Tanentzapf Guy G Schöck Frieder F Calderwood David A DA

Journal of cell science 20120919 Pt 23

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 acti ...[more]

PMID: 22992465

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