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Cited by 0Muscle Physiology and DisordersProtein Structure and DynamicsCardiomyopathy and Myosin Studies

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Zasp52’s differentially expressed intrinsically disordered region confers thin filament stability at the Z-disc

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Ho, Nikolai, Schöck, Frieder·2026·eLife
DOI 10.7554/elife.111101.3

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Abstract

The Drosophila 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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Metadata

Authors
Ho, N., & Schöck, F.
Affiliations
McGill University (CA)
Corresponding author
Schöck, Frieder
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2026-08-27
Volume
15
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.111101.3
OpenAlex
W7136051348
Cited by
0
References
4
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • eLife (acceptedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
Funders
Canadian Institutes of Health Research (project grant PJT-178114)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
Keywords
intrinsically disordered regions, Z-disc, indirect flight muscle, alternative splicing, actin, muscle contraction, flightlessness, Drosophila

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