Gα_q-Coupled Muscarinic Acetylcholine Receptors Enhance Nicotinic Acetylcholine Receptor Signaling inCaenorhabditis elegansMating Behavior

Abstract

In this study, we address why metabotropic and ionotropic cholinergic signaling pathways are used to facilitate motor behaviors. We demonstrate that a G␣ q -coupled muscarinic acetylcholine receptor (mAChR) signaling pathway enhances nicotinic acetylcholine receptor (nAChR) signaling to facilitate the insertion of the Caenorhabditis elegans male copulatory spicules into the hermaphrodite during mating. Previous studies showed that ACh (acetylcholine) activates nAChRs on the spicule protractor muscles to induce the attached spicules to extend from the tail. Using the mAChR agonist Oxo M (oxotremorine M), we identified a GAR-3(mAChR)-G␣ q pathway that promotes protractor muscle contraction by upregulating nAChR signaling before mating. GAR-3(mAChR) is expressed in the protractor muscles and in the spicule-associated SPC and PCB cholinergic neurons. However, ablation of these neurons or impairing cholinergic transmission reduces drug-induced spicule protraction, suggesting that drug-stimulated neurons directly activate muscle contraction. Behavioral analysis of gar-3 mutants indicates that, in wild-type males, GAR-3(mAChR) expression in the SPC and PCB neurons is required for the male to sustain rhythmic spicule muscle contractions during attempts to breach the vulva. We propose that the GAR-3(mAChR)/G␣ q pathway sensitizes the spicule neurons and muscles before and during mating so that the male can respond to hermaphrodite vulva efficiently.

Cell Excitability Necessary for Male Mating Behavior inCaenorhabditis elegansIs Coordinated by Interactions Between Big Current and Ether-A-Go-Go Family K+ Channels

“…To test this hypothesis, we measured the transcript levels of genes involved in regulating the excitability of cells used in male mating behavior and also of genes involved in more general cell processes. We analyzed acr-18 [nicotinic acetylcholine receptor (nAChR) a-subunit], gar-3 (ACh receptor coupled to ga q ), unc-29 (nAChR non-a-subunit), unc-43 (CaMKII), and cat-2 (tyrosine hydroxylase) as candidate genes that are enriched in excitable cells (Sulston et al 1975;Fleming et al 1997;Hwang et al 1999;Lints and Emmons 1999;Reiner et al 1999;Sze et al 2000;Garcia et al 2001;Mongan et al 2002;LeBoeuf et al 2007;Liu et al 2007bLiu et al , 2011. Neither acr-18 nor cat-2 transcript levels were increased in males as compared to hermaphrodites (Figure 3, C and D), although both were reduced in slo-1(rg432) males.…”

“…CaMKII's role in regulating transcription is well The SPC motor neuron innervates the protractor muscles and releases constant low levels of acetylcholine (ACh) to help maintain sex muscle excitability. ACh activates muscarinic ACh receptors, releasing Gaq that results in intracellular increase in Ca 2+ (Liu et al 2007b). This in turn activates CaMKII, which increases the transcription of K + channel genes to help lower the sex muscle excitability.…”

Reversal of Salt Preference Is Directed by the Insulin/PI3K and Gq/PKC Signaling inCaenorhabditis elegans

“…EGL-30 was suggested to be coupled with several G-protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChR) (Lackner et al 1999), a DOP-1 dopamine receptor (Chase et al 2004;Kindt et al 2007), GAR-3 mAChR (Liu et al 2007), and SER-3 octopamine receptor (Suo et al 2006). Although activation of EGL-30 and addition of a DAG analog promote salt attraction, it is unknown whether EGL-30 is required for the production of DAG in ASER.…”

Effects of the muscarinic agonist, 5-methylfurmethiodide, on contraction and electrophysiology of Ascaris suum muscle

“…GAR-3 is molecularly and pharmacologically more like mammalian muscarinic receptors and is sensitive to atropine. In C. elegans the GAR-3 receptor is coupled to and inhibits opening of a potassium channel and enhances nicotinic receptor function via a G αq protein in the male spicule muscle (Liu et al, 2007) but in the pharyngeal muscle GAR-3 stimulation enhances a calcium current (Steger and Avery, 2004).…”