Neuronally expressed Ras-family GTPase Di-Ras modulates synaptic activity in Caenorhabditis elegans

Minoru Tada, Keiko Gengyo-Ando, Tetsuo Kobayashi, Masamitsu Fukuyama, Shohei Mitani, Kenji Kontani, Toshiaki Katada

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Ras-family GTPases regulate a wide variety of cellular functions including cell growth and differentiation. Di-Ras, which belongs to a distinct subfamily of Ras-family GTPases, is expressed predominantly in brain, but the role of Di-Ras in nervous systems remains totally unknown. Here, we report that the Caenorhabditis elegans Di-Ras homologue drn-1 is expressed specifically in neuronal cells and involved in synaptic function at neuromuscular junctions. Loss of function of drn-1 conferred resistance to the acetylcholinesterase inhibitor aldicarb and partially suppressed the aldicarb-hypersensitive phenotypes of heterotrimeric G-protein mutants, in which acetylcholine release is up-regulated. drn-1 mutants displayed no apparent defects in the axonal distribution of the membrane-bound second messenger diacylglycerol (DAG), which is a key stimulator of acetylcholine release. Finally, we have identified EPAC-1, a C. elegans Epac homologue, as a binding partner for DRN-1. Deletion mutants of epac-1 displayed an aldicarb-resistant phenotype as drn-1 mutants. Genetic analysis of drn-1 and epac-1 showed that they acted in the same pathway to control acetylcholine release. Furthermore, DRN-1 and EPAC-1 were co-immunoprecipitated. These findings suggest that DRN-1 may function cooperatively with EPAC-1 to modulate synaptic activity in C. elegans.

Original languageEnglish
Pages (from-to)778-789
Number of pages12
JournalGenes to Cells
Issue number9
Publication statusPublished - 2012 Sep
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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