Zasp is required for the assembly of functional integrin adhesion sites.
The integrin family of heterodimeric transmembrane receptors mediates cell-matrix adhesion. Integrins often localize in highly organized structures, such as focal adhesions in tissue culture and myotendinous junctions in muscles. Our RNA interference screen for genes that prevent integrin-dependent cell spreading identifies Z band alternatively spliced PDZ-motif protein (zasp), encoding the only known Drosophila melanogaster Alp/Enigma PDZ-LIM domain protein. Zasp localizes to integrin adhesion sites and its depletion disrupts integrin adhesion sites. In tissues, Zasp colocalizes with betaPS integrin in myotendinous junctions and with alpha-actinin in muscle Z lines. Zasp also physically interacts with alpha-actinin. Fly larvae lacking Zasp do not form Z lines and fail to recruit alpha-actinin to the Z line. At the myotendinous junction, muscles detach in zasp mutants with the onset of contractility. Finally, Zasp interacts genetically with integrins, showing that it regulates integrin function. Our observations point to an important function for Zasp in the assembly of integrin adhesion sites both in cell culture and in tissues.
Jani
Klodiana
K
Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.
Schöck
Frieder
F
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005820:Genetic Testing; D016023:Integrins / Q000378:metabolism*; D060588:LIM Domain Proteins; D007814:Larva; D054792:Muscle, Striated / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D034622:RNA Interference; D013710:Tendons / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D016023:Integrins; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; C526450:Zasp52 protein, Drosophila