The Drosophila Z-disc Protein Z(210) Is an Adult Muscle Isoform of Zasp52, Which Is Required for Normal Myofibril Organization in Indirect Flight Muscles

The Z-disc is a critical anchoring point for thin filaments as they slide during muscle contraction. Therefore, identifying components of the Z-disc is critical for fully comprehending how myofibrils assemble and function. In the adult Drosophila musculature, the fibrillar indirect flight muscles accumulate a >200 kDa Z-disc protein termed Z(210), the identity of which has to date been unknown. Here, we use mass spectrometry and gene specific knockdown studies, to identify Z(210) as an adult isoform of the Z-disc protein Zasp52. The Zasp52 primary transcript is extensively alternatively spliced, and we describe its splicing pattern in the flight muscles, identifying a new Zasp52 isoform, which is the one recognized by the Z(210) antibody. We also demonstrate that Zasp52 is required for the association of α-actinin with the flight muscle Z-disc, and for normal sarcomere structure. These studies expand our knowledge of Zasp isoforms and their functions in muscle. Given the role of Zasp proteins in mammalian muscle development and disease, our results have relevance to mammalian muscle biology. Background: Several components of Drosophila flight muscles are not characterized. Results: The Z disc protein Z(210) is an adult isoform of Zasp52, and Zasp52 is required for sarcomere structure in adult muscles. Conclusion: Flight muscles utilize a novel Zasp52 isoform. Significance: Drosophila Zasp52 is homologous to human ZASP, which is a disease gene.