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Neuronally expressed R as‐family GTP ase D i‐ R as modulates synaptic activity in C aenorhabditis elegans
Author(s) -
Tada Minoru,
GengyoAndo Keiko,
Kobayashi Tetsuo,
Fukuyama Masamitsu,
Mitani Shohei,
Kontani Kenji,
Katada Toshiaki
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2012.01627.x
Subject(s) - caenorhabditis elegans , biology , heterotrimeric g protein , gtpase , microbiology and biotechnology , mutant , g protein , gq alpha subunit , biochemistry , signal transduction , gene
Ras‐family GTP ases regulate a wide variety of cellular functions including cell growth and differentiation. Di‐ R as, which belongs to a distinct subfamily of R as‐family GTP ases, is expressed predominantly in brain, but the role of Di‐Ras in nervous systems remains totally unknown. Here, we report that the C aenorhabditis elegans D i‐ R as 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 .