title: Zasp52, a Core Z-disc Protein in Drosophila Indirect Flight Muscles, Interacts with α-Actinin via an Extended PDZ Domain.
abstract: Z-discs are organizing centers that establish and maintain myofibril structure and function. Important Z-disc proteins are α-actinin, which cross-links actin thin filaments at the Z-disc and Zasp PDZ domain proteins, which directly interact with α-actinin. Here we investigate the biochemical and genetic nature of this interaction in more detail. Zasp52 is the major Drosophila Zasp PDZ domain protein, and is required for myofibril assembly and maintenance. We show by in vitro biochemistry that the PDZ domain plus a C-terminal extension is the only area of Zasp52 involved in the interaction with α-actinin. In addition, site-directed mutagenesis of 5 amino acid residues in the N-terminal part of the PDZ domain, within the PWGFRL motif, abolish binding to α-actinin, demonstrating the importance of this motif for α-actinin binding. Rescue assays of a novel Zasp52 allele demonstrate the crucial importance of the PDZ domain for Zasp52 function. Flight assays also show that a Zasp52 mutant suppresses the α-actinin mutant phenotype, indicating that both proteins are core structural Z-disc proteins required for optimal Z-disc function.
authors: Department of Biology, McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, CANADA.
authors: Kuo An
authors: KA
authors: Liao
authors: Department of Biology, McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, CANADA.
authors: Nicanor
authors: N
authors: González-Morales
authors: Department of Biology, McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, CANADA.
authors: Frieder
authors: http://orcid.org/0000-0002-1351-0574
authors: F
authors: Schöck
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000185:Actinin / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D005426:Flight, Animal; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009210:Myofibrils / Q000235:genetics* / Q000378:metabolism; D054731:PDZ Domains / Q000235:genetics; D011485:Protein Binding; D012518:Sarcomeres / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; C526450:Zasp52 protein, Drosophila; D000185:Actinin