Format

Send to

Choose Destination
Development. 2015 Mar 1;142(5):994-1005. doi: 10.1242/dev.115352.

Drosophila small heat shock protein CryAB ensures structural integrity of developing muscles, and proper muscle and heart performance.

Author information

1
GReD - INSERM U1103, CNRS UMR6293, Clermont Université, 28, place Henri Dunant, Clermont-Ferrand 63000, France Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wrocław, Sienkiewicza 21, Wrocław 50-335, Poland.
2
Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wrocław, Sienkiewicza 21, Wrocław 50-335, Poland.
3
GReD - INSERM U1103, CNRS UMR6293, Clermont Université, 28, place Henri Dunant, Clermont-Ferrand 63000, France.
4
Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
5
GReD - INSERM U1103, CNRS UMR6293, Clermont Université, 28, place Henri Dunant, Clermont-Ferrand 63000, France teresa.jagla@udamail.fr.

Abstract

Molecular chaperones, such as the small heat shock proteins (sHsps), maintain normal cellular function by controlling protein homeostasis in stress conditions. However, sHsps are not only activated in response to environmental insults, but also exert developmental and tissue-specific functions that are much less known. Here, we show that during normal development the Drosophila sHsp CryAB [L(2)efl] is specifically expressed in larval body wall muscles and accumulates at the level of Z-bands and around myonuclei. CryAB features a conserved actin-binding domain and, when attenuated, leads to clustering of myonuclei and an altered pattern of sarcomeric actin and the Z-band-associated actin crosslinker Cheerio (filamin). Our data suggest that CryAB and Cheerio form a complex essential for muscle integrity: CryAB colocalizes with Cheerio and, as revealed by mass spectrometry and co-immunoprecipitation experiments, binds to Cheerio, and the muscle-specific attenuation of cheerio leads to CryAB-like sarcomeric phenotypes. Furthermore, muscle-targeted expression of CryAB(R120G), which carries a mutation associated with desmin-related myopathy (DRM), results in an altered sarcomeric actin pattern, in affected myofibrillar integrity and in Z-band breaks, leading to reduced muscle performance and to marked cardiac arrhythmia. Taken together, we demonstrate that CryAB ensures myofibrillar integrity in Drosophila muscles during development and propose that it does so by interacting with the actin crosslinker Cheerio. The evidence that a DRM-causing mutation affects CryAB muscle function and leads to DRM-like phenotypes in the fly reveals a conserved stress-independent role of CryAB in maintaining muscle cell cytoarchitecture.

KEYWORDS:

Cheerio; CryAB; Drosophila; Heart; Muscle; sHsp

PMID:
25715399
DOI:
10.1242/dev.115352
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center