title: Spillover transmission is mediated by the excitatory GABA receptor LGC-35 in C. elegans.
abstract: Under most circumstances, GABA activates chloride-selective channels and thereby inhibits neuronal activity. Here, we identify a GABA receptor in the nematode Caenorhabditis elegans that conducts cations and is therefore excitatory. Expression in Xenopus oocytes demonstrates that LGC-35 is a homopentameric cation-selective receptor of the cys-loop family exclusively activated by GABA. Phylogenetic analysis suggests that LGC-35 evolved from GABA-A receptors, but the pore-forming domain contains novel molecular determinants that confer cation selectivity. LGC-35 is expressed in muscles and directly mediates sphincter muscle contraction in the defecation cycle in hermaphrodites, and spicule eversion during mating in the male. In the locomotory circuit, GABA release directly activates chloride channels on the muscle to cause muscle relaxation. However, GABA spillover at these synapses activates LGC-35 on acetylcholine motor neurons, which in turn cause muscles to contract, presumably to drive wave propagation along the body. These studies demonstrate that both direct and indirect excitatory GABA signaling plays important roles in regulating neuronal circuit function and behavior in C. elegans.
authors: Program in Neuroscience, University of Utah School of Medicine, Salt Lake City, Utah 84132, Department of Biology, University of Utah, Salt Lake City, Utah 84132.
authors: Meghan A
authors: MA
authors: Jobson
authors: Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109.
authors: Chris M
authors: CM
authors: Valdez
authors: Department of Biology, University of Utah, Salt Lake City, Utah 84132.
authors: Jann
authors: J
authors: Gardner
authors: Department of Biology, Texas A&M University, College Station, Texas 77843, Howard Hughes Medical Institute, Texas A&M University, College Station, Texas 77843.
authors: L Rene
authors: LR
authors: Garcia
authors: Program in Neuroscience, University of Utah School of Medicine, Salt Lake City, Utah 84132, Department of Biology, University of Utah, Salt Lake City, Utah 84132, Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84132, and asimbeg@umich.edu jorgensen@biology.utah.edu.
authors: Erik M
authors: EM
authors: Jorgensen
authors: Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109, asimbeg@umich.edu jorgensen@biology.utah.edu.
authors: Asim A
authors: AA
authors: Beg
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D003307:Copulation / Q000502:physiology; D003672:Defecation; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009132:Muscles / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects; D018079:Receptors, GABA / Q000235:genetics / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D029742:Caenorhabditis elegans Proteins; C000596713:LGC-35 protein, C elegans; D018079:Receptors, GABA; D000109:Acetylcholine
keywords: C. elegans; GABA; cys-loop; ion selectivity