Key result
Deletion of the intrinsically disordered region encoded by exon 15e in Zasp52 resulted in flightlessness and structural indirect flight muscle defects in Drosophila.
The intrinsically disordered region of Zasp52 is essential for maintaining thin filament stability and structural integrity at the Z-disc in Drosophila indirect flight muscle.
Zasp52 IDR supports Z-disc integrity in high-force muscle; leaves open relevance to human cardiac or skeletal myopathies.
scaffolding protein Zasp52 is required to maintain structure at the muscle Z-disc, which experiences strong forces during contraction. It is alternatively spliced into many isoforms, some of which contain a long intrinsically disordered region (IDR). We show that this region is primarily expressed in the indirect flight muscle (IFM) and is required for maintaining the integrity of the Z-disc. Deleting the IDR-encoding exon 15e results in flightlessness and structural IFM defects, including sarcomere bending at the Z-disc and an inability to de-contract. These defects are indicative of a lack of proper thin filament anchoring to the Z-disc. This is further supported by a genetic interaction between exon 15e and actin. Fluorescence recovery after photobleaching of an isoform lacking exon 15e shows that the IDR is required for maintaining Zasp52 at the Z-disc and thereby stabilizing Z-discs. Lastly, we can rescue these phenotypes by restricting IFM use. Together, these results suggest that Zasp52's IDR confers thin filament stability at the Z-disc of IFM.
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Ho et al. (2026) studied Drosophila muscle function. Zasp52 exon 15e deletion vs. Wild-type control was evaluated. Deletion of the intrinsically disordered region encoded by exon 15e in Zasp52 resulted in flightlessness and structural indirect flight muscle defects in Drosophila.
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