Alp/Enigma Family Proteins Cooperate in Z-Disc Formation and Myofibril Assembly: e1003342

• Published in: PLoS genetics 2013-03, Vol.9 (3)
• Main Authors: Katzemich, Anja, Liao, Kuo An, Czerniecki, Stefan, Schöck, Frieder
• Format: Article
• Language: English
• Subjects: Amino acids; Defects; Drosophila; Insects; Medical research; Microscopy; Mutation; Proteins; Vertebrates
• ISSN: 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1003342

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.