Presynaptic UNC-31 (CAPS) is required to activate the G alpha(s) pathway of the Caenorhabditis elegans synaptic signaling network.
C. elegans mutants lacking the dense-core vesicle priming protein UNC-31 (CAPS) share highly similar phenotypes with mutants lacking a neuronal G alpha(s) pathway, including strong paralysis despite exhibiting near normal levels of steady-state acetylcholine release as indicated by drug sensitivity assays. Our genetic analysis shows that UNC-31 and neuronal G alpha(s) are different parts of the same pathway and that the UNC-31/G alpha(s) pathway is functionally distinct from the presynaptic G alpha(q) pathway with which it interacts. UNC-31 acts upstream of G alpha(s) because mutations that activate the G alpha(s) pathway confer similar levels of strongly hyperactive, coordinated locomotion in both unc-31 null and (+) backgrounds. Using cell-specific promoters, we show that both UNC-31 and the G alpha(s) pathway function in cholinergic motor neurons to regulate locomotion rate. Using immunostaining we show that UNC-31 is often concentrated at or near active zones of cholinergic motor neuron synapses. Our data suggest that presynaptic UNC-31 activity, likely acting via dense-core vesicle exocytosis, is required to locally activate the neuronal G alpha(s) pathway near synaptic active zones.
Charlie
Nicole K
NK
Program in Molecular, Cell and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Schade
Michael A
MA
Thomure
Angela M
AM
Miller
Kenneth G
KG
D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000235:genetics / Q000502:physiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000502:physiology; D010641:Phenotype; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; C107581:UNC-31 protein, C elegans; D000448:Aldicarb; D019205:GTP-Binding Protein alpha Subunits, Gs