title: 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 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.
authors.affiliation: Departments of Pharmacology and Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520,  USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouaouina
authors.forename: Klodiana
authors.initials: K
authors.lastname: Jani
authors.forename: Jenny Y
authors.initials: JY
authors.lastname: Long
authors.forename: Stefan
authors.initials: S
authors.lastname: Czerniecki
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Morse
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Ellis
authors.forename: Guy
authors.initials: G
authors.lastname: Tanentzapf
authors.forename: Frieder
authors.initials: F
authors.lastname: Schöck
authors.forename: David A
authors.initials: DA
authors.lastname: Calderwood
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D016608:Talin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D039081:Integrin alpha5beta1; D016023:Integrins; D016608:Talin; C526450:Zasp52 protein, Drosophila