Presynaptic UNC-31 (CAPS) Is Required to Activate the Gαs Pathway of the Caenorhabditis elegans Synaptic Signaling Network

• Published in: Genetics (Austin) Vol. 172; no. 2; pp. 943 - 961
• Main Authors: Charlie, Nicole K, Schade, Michael A, Thomure, Angela M, Miller, Kenneth G
• Format: Journal Article
• Language: English
• Published: Copyright © 2006 by the Genetics Society of America 01.02.2006
• Subjects: Investigations
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.105.049577

Abstract C. elegans mutants lacking the dense-core vesicle priming protein UNC-31 (CAPS) share highly similar phenotypes with mutants lacking a neuronal Gαs 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 Gαs are different parts of the same pathway and that the UNC-31/Gαs pathway is functionally distinct from the presynaptic Gαq pathway with which it interacts. UNC-31 acts upstream of Gαs because mutations that activate the Gαs 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 Gαs 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 Gαs pathway near synaptic active zones.