Reference - Detail
|Author||Tada M, Gengyo-Ando K, Kobayashi T, Fukuyama M, Mitani S, Kontani K, Katada T.|
|Title||Neuronally expressed Ras-family GTPase Di-Ras modulates synaptic activity in Caenorhabditis elegans.|
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.
|MeSH||Acetylcholine / genetics Acetylcholine / metabolism Aldicarb / pharmacology Amino Acid Sequence Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / enzymology* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cholinergic Neurons / drug effects Cholinergic Neurons / enzymology* Cholinergic Neurons / physiology Cholinesterase Inhibitors / pharmacology Drug Resistance GTP Phosphohydrolases / genetics GTP Phosphohydrolases / metabolism* GTP-Binding Protein alpha Subunits, Gi-Go / genetics GTP-Binding Protein alpha Subunits, Gi-Go / metabolism Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism Immunoprecipitation / methods Neuromuscular Junction / drug effects Neuromuscular Junction / genetics Neuromuscular Junction / metabolism Phenotype Protein Interaction Mapping Sequence Deletion Synaptic Transmission*|
|WOS Category||GENETICS & HEREDITY CELL BIOLOGY|
|C.elegans||tm3203 tm2916 tm2926 tm3214|