Convergent, RIC-8-dependent Galpha signaling pathways in the Caenorhabditis elegans synaptic signaling network.
We used gain-of-function and null synaptic signaling network mutants to investigate the relationship of the G alpha(q) and G alpha(s) pathways to synaptic vesicle priming and to each other. Genetic epistasis studies using G alpha(q) gain-of-function and null mutations, along with a mutation that blocks synaptic vesicle priming and the synaptic vesicle priming stimulator phorbol ester, suggest that the G alpha(q) pathway generates the core, obligatory signals for synaptic vesicle priming. In contrast, the G alpha(s) pathway is not required for the core priming function, because steady-state levels of neurotransmitter release are not significantly altered in animals lacking a neuronal G alpha(s) pathway, even though these animals are strongly paralyzed as a result of functional (nondevelopmental) defects. However, our genetic analysis indicates that these two functionally distinct pathways converge and that they do so downstream of DAG production. Further linking the two pathways, our epistasis analysis of a ric-8 null mutant suggests that RIC-8 (a receptor-independent G alpha guanine nucleotide exchange factor) is required to maintain both the G alpha(q) vesicle priming pathway and the neuronal G alpha(s) pathway in a functional state. We propose that the neuronal G alpha(s) pathway transduces critical positional information onto the core G alpha(q) pathway to stabilize the priming of selected synapses that are optimal for locomotion.
Reynolds
Nicole K
NK
Program in Molecular, Cell and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Schade
Michael A
MA
Miller
Kenneth G
KG
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000235:genetics*; D019076:Transgenes
D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; D015801:Helminth Proteins; D009687:Nuclear Proteins; C413418:RIC-8 protein, C elegans; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11