論文 - 詳細
| RRC ID | 53536 |
|---|---|
| 著者 | Takayanagi-Kiya S, Jin Y. |
| タイトル | Altered Function of the DnaJ Family Cochaperone DNJ-17 Modulates Locomotor Circuit Activity in a Caenorhabditis elegans Seizure Model. |
| ジャーナル | G3 (Bethesda) |
| Abstract |
The highly conserved cochaperone DnaJ/Hsp40 family proteins are known to interact with molecular chaperone Hsp70, and can regulate many cellular processes including protein folding, translocation, and degradation. In studies of Caenorhabditis elegans locomotion mutants, we identified a gain-of-function (gf) mutation in dnj-17 closely linked to the widely used e156 null allele of C. elegans GAD (glutamic acid decarboxylase) unc-25 dnj-17 encodes a DnaJ protein orthologous to human DNAJA5. In C. elegans DNJ-17 is a cytosolic protein and is broadly expressed in many tissues. dnj-17(gf) causes a single amino acid substitution in a conserved domain, and behaves as a hypermorphic mutation. The effect of this dnj-17(gf) is most prominent in mutants lacking GABA synaptic transmission. In a seizure model caused by a mutation in the ionotropic acetylcholine receptor acr-2(gf), dnj-17(gf) exacerbates the convulsion phenotype in conjunction with absence of GABA. Null mutants of dnj-17 show mild resistance to aldicarb, while dnj-17(gf) is hypersensitive. These results highlight the importance of DnaJ proteins in regulation of C. elegans locomotor circuit, and provide insights into the in vivo roles of DnaJ proteins in humans. |
| 巻・号 | 6(7) |
| ページ | 2165-71 |
| 公開日 | 2016-7-7 |
| DOI | 10.1534/g3.116.028928 |
| PII | g3.116.028928 |
| PMID | 27185401 |
| PMC | PMC4938669 |
| MeSH | Aldicarb / pharmacology Amino Acid Sequence Amino Acid Substitution Animals Behavior, Animal Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cholinesterase Inhibitors / pharmacology Conserved Sequence Disease Models, Animal Gene Expression Regulation Glutamate Decarboxylase / genetics Glutamate Decarboxylase / metabolism HSP40 Heat-Shock Proteins / deficiency HSP40 Heat-Shock Proteins / genetics* HSP40 Heat-Shock Proteins / metabolism Humans Locomotion Receptors, Nicotinic / deficiency Receptors, Nicotinic / genetics Seizures / genetics* Seizures / metabolism Seizures / physiopathology Sequence Alignment Sequence Homology, Amino Acid Synaptic Transmission / genetics* gamma-Aminobutyric Acid / deficiency |
| IF | 2.781 |
| 引用数 | 1 |
| リソース情報 | |
| 線虫 | tm570 tm4063 |