Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
Abstract
Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles. Within a muscle type, myofibril diameter is highly invariant and contributes to its physiological properties, yet little is known about the underlying mechanisms setting myofibril diameter. Here we show that the PDZ and LIM domain protein Zasp, a structural component of Z-discs, mediates Z-disc and thereby myofibril growth through protein oligomerization. Oligomerization is induced by an interaction of its ZM domain with LIM domains. Oligomerization is terminated upon upregulation of shorter Zasp isoforms which lack LIM domains at later developmental stages. The balance between these two isoforms, which we call growing and blocking isoforms sets the stereotyped diameter of myofibrils. If blocking isoforms dominate, myofibrils become smaller. If growing isoforms dominate, myofibrils and Z-discs enlarge, eventually resulting in large pathological aggregates that disrupt muscle function.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (MOP-142475)
- Nicanor González-Morales
- Yu Shu Xiao
- Matthew Aaron Schilling
- Océane Marescal
- Kuo An Liao
Canadian Institutes of Health Research (PJT-155995)
- Nicanor González-Morales
- Yu Shu Xiao
- Matthew Aaron Schilling
- Océane Marescal
- Kuo An Liao
Natural Sciences and Engineering Research Council of Canada (RGPIN 2016-06793)
- Nicanor González-Morales
- Yu Shu Xiao
- Matthew Aaron Schilling
- Océane Marescal
- Kuo An Liao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, González-Morales et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,315
- views
-
- 291
- downloads
-
- 31
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.