CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors

eLife

Janet E Richmond¹  Manuela D'Alessandro²  Thomas Boulin²  Jean-Louis Bessereau²  Vincent Gache²  Magali Richard²  Christian Stigloher² 

[1] Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States;Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, Lyon, France;

关键词: Cys-loop receptor;    acetylcholine receptor (AChR);    neuromuscular junction (NMJ);    protein disulphide isomerase (PDI);    endoplasmic reticulum (ER);   

DOI  :  10.7554/eLife.39649

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown