| RRC ID |
59331
|
| 著者 |
D'Alessandro M, Richard M, Stigloher C, Gache V, Boulin T, Richmond JE, Bessereau JL.
|
| タイトル |
CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors.
|
| ジャーナル |
Elife
|
| 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.
|
| 巻・号 |
7
|
| 公開日 |
2018-11-7
|
| DOI |
10.7554/eLife.39649
|
| PII |
39649
|
| PMID |
30407909
|
| PMC |
PMC6245729
|
| MeSH |
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism
Cell Line
Extracellular Matrix Proteins / genetics
Extracellular Matrix Proteins / metabolism
Gene Knockdown Techniques
Genetic Complementation Test
Heart Defects, Congenital
Mice
Muscle Cells
Protein Binding
Protein Disulfide-Isomerases / genetics
Protein Disulfide-Isomerases / metabolism*
Protein Multimerization
Receptors, Cholinergic / metabolism*
Synapses / metabolism*
|
| IF |
7.551
|
| 引用数 |
1
|
| リソース情報 |
| 線虫 |
tm3993 |
