title: Alp/Enigma family proteins cooperate in Z-disc formation and myofibril assembly.
abstract: The Drosophila Alp/Enigma family protein Zasp52 localizes to myotendinous junctions and Z-discs. It is required for terminal muscle differentiation and muscle attachment. Its vertebrate ortholog ZASP/Cypher also localizes to Z-discs, interacts with α-actinin through its PDZ domain, and is involved in Z-disc maintenance. Human mutations in ZASP cause myopathies and cardiomyopathies. Here we show that Drosophila Zasp52 is one of the earliest markers of Z-disc assembly, and we use a Zasp52-GFP fusion to document myofibril assembly by live imaging. We demonstrate that Zasp52 is required for adult Z-disc stability and pupal myofibril assembly. In addition, we show that two closely related proteins, Zasp66 and the newly identified Zasp67, are also required for adult Z-disc stability and are participating with Zasp52 in Z-disc assembly resulting in more severe, synergistic myofibril defects in double mutants. Zasp52 and Zasp66 directly bind to α-actinin, and they can also form a ternary complex. Our results indicate that Alp/Enigma family members cooperate in Z-disc assembly and myofibril formation; and we propose, based on sequence analysis, a novel class of PDZ domain likely involved in α-actinin binding.
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Anja
authors.initials: A
authors.lastname: Katzemich
authors.forename: Kuo An
authors.initials: KA
authors.lastname: Liao
authors.forename: Stefan
authors.initials: S
authors.lastname: Czerniecki
authors.forename: Frieder
authors.initials: F
authors.lastname: Schöck
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics*; D009132:Muscles / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009210:Myofibrils / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054731:PDZ Domains / Q000235:genetics; D011485:Protein Binding; D012518:Sarcomeres / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; C526450:Zasp52 protein, Drosophila; C581617:Zasp67 protein, Drosophila; D000185:Actinin