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  • 标题:Extrasynaptic acetylcholine signaling through a muscarinic receptor regulates cell migration
  • 本地全文:下载
  • 作者:Mihoko Kato ; Irina Kolotuev ; Alexandre Cunha
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2021
  • 卷号:118
  • 期号:1
  • 页码:1
  • DOI:10.1073/pnas.1904338118
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Acetylcholine (ACh) promotes various cell migrations in vitro, but there are few investigations into this nonsynaptic role of ACh signaling in vivo. Here we investigate the function of a muscarinic receptor on an epithelial cell migration in Caenorhabditis elegans . We show that the migratory gonad leader cell, the linker cell (LC), uses an M1/M3/M5-like muscarinic ACh receptor GAR-3 to receive extrasynaptic ACh signaling from cholinergic neurons for its migration. Either the loss of the GAR-3 receptor in the LC or the inhibition of ACh release from cholinergic neurons resulted in migratory path defects. The overactivation of the GAR-3 muscarinic receptor caused the LC to reverse its orientation through its downstream effectors Gαq/ egl-30 , PLCβ/ egl-8 , and TRIO/ unc-73 . This reversal response only occurred in the fourth larval stage, which corresponds to the developmental time when the GAR-3::yellow fluorescent protein receptor in the membrane relocalizes from a uniform to an asymmetric distribution. These findings suggest a role for the GAR-3 muscarinic receptor in determining the direction of LC migration.
  • 关键词:cell migration ; muscarinic receptor ; acetylcholine
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