TY - JOUR TI - CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors AU - D'Alessandro, Manuela AU - Richard, Magali AU - Stigloher, Christian AU - Gache, Vincent AU - Boulin, Thomas AU - Richmond, Janet E AU - Bessereau, Jean-Louis A2 - Hobert, Oliver A2 - Westbrook, Gary L VL - 7 PY - 2018 DA - 2018/11/08 SP - e39649 C1 - eLife 2018;7:e39649 DO - 10.7554/eLife.39649 UR - https://doi.org/10.7554/eLife.39649 AB - 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. KW - Cys-loop receptor KW - acetylcholine receptor (AChR) KW - neuromuscular junction (NMJ) KW - protein disulphide isomerase (PDI) KW - endoplasmic reticulum (ER) JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -