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J Neurosci
2015 Feb 11;356:2803-16. doi: 10.1523/JNEUROSCI.4557-14.2015.
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Spillover transmission is mediated by the excitatory GABA receptor LGC-35 in C. elegans.
Jobson MA
,
Valdez CM
,
Gardner J
,
Garcia LR
,
Jorgensen EM
,
Beg AA
.
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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.
Amin,
GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital.
1993, Pubmed,
Xenbase
Amin,
GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital.
1993,
Pubmed
,
Xenbase
Bamber,
The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor.
1999,
Pubmed
,
Xenbase
Beg,
EXP-1 is an excitatory GABA-gated cation channel.
2003,
Pubmed
,
Xenbase
Beg,
Protons act as a transmitter for muscle contraction in C. elegans.
2008,
Pubmed
Boileau,
Mapping the agonist binding site of the GABAA receptor: evidence for a beta-strand.
1999,
Pubmed
,
Xenbase
Boileau,
GABA(A) receptor beta 2 Tyr97 and Leu99 line the GABA-binding site. Insights into mechanisms of agonist and antagonist actions.
2002,
Pubmed
,
Xenbase
Chen,
Wiring optimization can relate neuronal structure and function.
2006,
Pubmed
Corringer,
Mutational analysis of the charge selectivity filter of the alpha7 nicotinic acetylcholine receptor.
1999,
Pubmed
,
Xenbase
Croll,
Behavioural analysis of nematode movement.
1975,
Pubmed
ECCLES,
Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones.
1954,
Pubmed
Frøkjaer-Jensen,
Targeted gene deletions in C. elegans using transposon excision.
2010,
Pubmed
Galzi,
Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic.
1992,
Pubmed
,
Xenbase
Garcia,
Regulation of distinct muscle behaviors controls the C. elegans male's copulatory spicules during mating.
2001,
Pubmed
Garcia,
Caenorhabditis elegans UNC-103 ERG-like potassium channel regulates contractile behaviors of sex muscles in males before and during mating.
2003,
Pubmed
Gunthorpe,
Conversion of the ion selectivity of the 5-HT(3a) receptor from cationic to anionic reveals a conserved feature of the ligand-gated ion channel superfamily.
2001,
Pubmed
Hnasko,
Neurotransmitter corelease: mechanism and physiological role.
2012,
Pubmed
Hodgkin,
Male Phenotypes and Mating Efficiency in CAENORHABDITIS ELEGANS.
1983,
Pubmed
Imoto,
Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.
1988,
Pubmed
,
Xenbase
Jarrell,
The connectome of a decision-making neural network.
2012,
Pubmed
Jensen,
The beta subunit determines the ion selectivity of the GABAA receptor.
2002,
Pubmed
Jensen,
Mutational studies using a cation-conducting GABAA receptor reveal the selectivity determinants of the Cys-loop family of ligand-gated ion channels.
2005,
Pubmed
Jensen,
Charge selectivity of the Cys-loop family of ligand-gated ion channels.
2005,
Pubmed
Jin,
The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development.
1999,
Pubmed
Jones,
The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans.
2008,
Pubmed
Jospin,
A neuronal acetylcholine receptor regulates the balance of muscle excitation and inhibition in Caenorhabditis elegans.
2009,
Pubmed
,
Xenbase
Kamath,
Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.
2003,
Pubmed
Keramidas,
Cation-selective mutations in the M2 domain of the inhibitory glycine receptor channel reveal determinants of ion-charge selectivity.
2002,
Pubmed
Keramidas,
M2 pore mutations convert the glycine receptor channel from being anion- to cation-selective.
2000,
Pubmed
Lee,
Role of ACh-GABA cotransmission in detecting image motion and motion direction.
2010,
Pubmed
Liu,
Sensory regulation of male mating behavior in Caenorhabditis elegans.
1995,
Pubmed
Liu,
Regulation of a periodic motor program in C. elegans.
1994,
Pubmed
Liu,
A cholinergic-regulated circuit coordinates the maintenance and bi-stable states of a sensory-motor behavior during Caenorhabditis elegans male copulation.
2011,
Pubmed
Mahoney,
Analysis of synaptic transmission in Caenorhabditis elegans using an aldicarb-sensitivity assay.
2006,
Pubmed
Maruyama,
cRACE: a simple method for identification of the 5' end of mRNAs.
1995,
Pubmed
McIntire,
The GABAergic nervous system of Caenorhabditis elegans.
1993,
Pubmed
McIntire,
Genes required for GABA function in Caenorhabditis elegans.
1993,
Pubmed
Mello,
Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.
1991,
Pubmed
Miller,
A genetic selection for Caenorhabditis elegans synaptic transmission mutants.
1996,
Pubmed
Mullen,
The Caenorhabditis elegans snf-11 gene encodes a sodium-dependent GABA transporter required for clearance of synaptic GABA.
2006,
Pubmed
Nishiyama,
Pure spillover transmission between neurons.
2007,
Pubmed
Peden,
Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans.
2013,
Pubmed
Pirri,
A tyramine-gated chloride channel coordinates distinct motor programs of a Caenorhabditis elegans escape response.
2009,
Pubmed
,
Xenbase
Putrenko,
A family of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans.
2005,
Pubmed
Ranganathan,
MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans.
2000,
Pubmed
,
Xenbase
Reiner,
Reversal of a muscle response to GABA during C. elegans male development.
1995,
Pubmed
Ringstad,
Ligand-gated chloride channels are receptors for biogenic amines in C. elegans.
2009,
Pubmed
,
Xenbase
Rossi,
Spillover-mediated transmission at inhibitory synapses promoted by high affinity alpha6 subunit GABA(A) receptors and glomerular geometry.
1998,
Pubmed
Schuske,
The GABA nervous system in C. elegans.
2004,
Pubmed
Sigel,
Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels.
1992,
Pubmed
,
Xenbase
Szapiro,
Multiple climbing fibers signal to molecular layer interneurons exclusively via glutamate spillover.
2007,
Pubmed
Thomas,
Genetic analysis of defecation in Caenorhabditis elegans.
1990,
Pubmed
Thompson,
The structural basis of function in Cys-loop receptors.
2010,
Pubmed
Wagner,
Structure and dynamics of the GABA binding pocket: A narrowing cleft that constricts during activation.
2001,
Pubmed
,
Xenbase
Wang,
Track-a-worm, an open-source system for quantitative assessment of C. elegans locomotory and bending behavior.
2013,
Pubmed
Weber,
Ion currents of Xenopus laevis oocytes: state of the art.
1999,
Pubmed
,
Xenbase
Westh-Hansen,
Decreased agonist sensitivity of human GABA(A) receptors by an amino acid variant, isoleucine to valine, in the alpha1 subunit.
1997,
Pubmed
Westh-Hansen,
Arginine residue 120 of the human GABAA receptor alpha 1, subunit is essential for GABA binding and chloride ion current gating.
1999,
Pubmed
White,
The structure of the nervous system of the nematode Caenorhabditis elegans.
1986,
Pubmed
Wotring,
Charge scan reveals an extended region at the intracellular end of the GABA receptor pore that can influence ion selectivity.
2008,
Pubmed
,
Xenbase
Wotring,
Mutations at the GABA receptor selectivity filter: a possible role for effective charges.
2003,
Pubmed
,
Xenbase
Yassin,
Characterization of the deg-3/des-2 receptor: a nicotinic acetylcholine receptor that mutates to cause neuronal degeneration.
2001,
Pubmed
,
Xenbase
