Key result
Uchmaz knockout disrupts sarcomeric Z-discs and causes flightless muscle dysfunction in Drosophila.
Why the study?
Many structural components of Z-discs that define sarcomere boundaries and anchor actin filaments in muscle remain uncharacterized.
Identification of Uchmaz as a critical component for Z-disc assembly and muscle function in Drosophila provides insights into conserved mechanisms relevant to human muscular dystrophies.
Uchmaz is required for sarcomere organization in Drosophila flight muscle; leaves open its role in mammalian cardiac Z-disc function.
Z-discs define sarcomere boundaries and anchor actin filaments in muscle, yet many structural components remain uncharacterized. In this paper, we identify three new members of the Alp/Enigma family in Drosophila , including Uchmaz (CG42319), a PDZ domain-containing protein, that we characterize in detail. We used CRISPR/Cas9 to generate multiple uchmaz knockout alleles, which are viable but result in a flightless phenotype. Mutants exhibit disrupted sarcomere organization in the indirect flight muscles (IFMs), including fragmented and misaligned Z-discs and reduced accumulation of α-Actinin and other Z-disc markers. We find that Uchmaz localizes to the Z-disc, associates with α-Actinin, and is dependent upon α-Actinin for its localization to the Z-disc. These results identify Uchmaz as a component of IFM myofibril architecture required for muscle function. Since a human ortholog of uchmaz , PDLIM2 , is associated with severe muscle dysfunction in muscular dystrophies and myofibrillar myopathy, our studies provide insight into conserved mechanisms of Z-disc assembly and its relevance to human muscle disease.
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Robinson et al. (2026) studied muscle dysfunction (Drosophila model). uchmaz knockout was evaluated on sarcomere organization and muscle function. Uchmaz knockout in Drosophila resulted in a flightless phenotype with disrupted sarcomere organization, fragmented Z-discs, and reduced accumulation of α-Actinin.
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