CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors
- University of Lyon - INSERM - CNRS, France
- University of Illinois at Chicago, United States
Abstract
The assembly of neurotransmitter receptors in the endoplasmic reticulum limits the number of receptors delivered to the plasma membrane, ultimately controlling neurotransmitter sensitivity and synaptic transfer function. In a forward genetic screen conducted in the nematode C. elegans, we identified crld-1 as a gene required for the synaptic expression of ionotropic acetylcholine receptors (AChR). We demonstrated that the CRLD-1A isoform is a membrane-associated ER-resident protein disulfide isomerase (PDI). It physically interacts with AChRs and promotes the assembly of AChR subunits in the ER. Mutations of Creld1, the human ortholog of crld-1a, are responsible for developmental cardiac defects. We showed that Creld1 knockdown in mouse muscle cells decreased surface expression of AChRs and that expression of mouse Creld1 in C. elegans rescued crld-1a mutant phenotypes. Altogether these results identify a novel and evolutionarily-conserved maturational enhancer of AChR biogenesis, which controls the abundance of functional receptors at the cell surface.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Christian Stigloher
JeanLouis Bessereau
Funding
Association Française contre les Myopathies (Post-doctoral Fellowship 16451)
- Manuela D'Alessandro
European Molecular Biology Organization (Long term Post-doctoral fellowship)
- Christian Stigloher
Institut National de la Santé et de la Recherche Médicale (Junior Grant)
- Thomas Boulin
Association Française contre les Myopathies (Myoneuralp)
- JeanLouis Bessereau
Deutscher Akademischer Austauschdienst (Postdoctoral Program of the German Academic Exchange Service)
- Christian Stigloher
Fédération pour la Recherche sur le Cerveau (Operation Espoir en tête 2013)
- JeanLouis Bessereau
Fondation ARC pour la Recherche sur le Cancer (4th year PhD program 2011)
- Magali Richard
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, D'Alessandro 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.
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CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors
eLife 7:e39649.
https://doi.org/10.7554/eLife.39649
