A novel Drosophila ALP/Enigma protein binds to Alpha-actinin to promote sarcomere assembly
- 1Department of Biology, San Diego State University, San Diego, CA 92182
Abstract
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-disk markers. We find that Uchmaz localizes to the Z-disk, associates with α-Actinin, and is dependent upon α-Actinin for its localization to the Z-disk. 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-disk assembly and its relevance to human muscle disease.
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BibTeX
@article{robinson2026novel,
title = {{A novel Drosophila ALP/Enigma protein binds to Alpha-actinin to promote sarcomere assembly}},
author = {Ebru Robinson and Yiannis Alvarado and Sarah Mason and Shayla Tran and Richard M. Cripps},
journal = {Molecular Biology of the Cell},
year = {2026},
month = oct,
doi = {10.1091/mbc.e26-06-0293},
url = {https://doi.org/10.1091/mbc.e26-06-0293},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A novel Drosophila ALP/Enigma protein binds to Alpha-actinin to promote sarcomere assembly
AU - Ebru Robinson
AU - Yiannis Alvarado
AU - Sarah Mason
AU - Shayla Tran
AU - Richard M. Cripps
PY - 2026
DA - 2026/10/30
JO - Molecular Biology of the Cell
DO - 10.1091/mbc.e26-06-0293
UR - https://doi.org/10.1091/mbc.e26-06-0293
AB - 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-disk markers. We find that Uchmaz localizes to the Z-disk, associates with α-Actinin, and is dependent upon α-Actinin for its localization to the Z-disk. 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-disk assembly and its relevance to human muscle disease.
SN - 1059-1524
SN - 1939-4586
ER -