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Heterogeneous expression of GABA receptor-like subunits LCCH3 and GRD reveals functional diversity of GABA receptors in the honeybee Apis mellifera.
Henry C
,
Cens T
,
Charnet P
,
Cohen-Solal C
,
Collet C
,
van-Dijk J
,
Guiramand J
,
de Jésus-Ferreira MC
,
Menard C
,
Mokrane N
,
Roussel J
,
Thibault JB
,
Vignes M
,
Rousset M
.
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BACKGROUND AND PURPOSE: Despite a growing awareness, annual losses of honeybee colonies worldwide continue to reach threatening levels for food safety and global biodiversity. Among the biotic and abiotic stresses probably responsible for these losses, pesticides, including those targeting ionotropic GABA receptors, are one of the major drivers. Most insect genomes include the ionotropic GABA receptor subunit gene, Rdl, and two GABA-like receptor subunit genes, Lcch3 and Grd. Most studies have focused on Rdl which forms homomeric GABA-gated chloride channels, and a complete analysis of all possible molecular combinations of GABA receptors is still lacking.
EXPERIMENTAL APPROACH: We cloned the Rdl, Grd, and Lcch3 genes of Apis mellifera and systematically characterized the resulting GABA receptors expressed in Xenopus oocytes, using electrophysiological assays, fluorescence microscopy and co-immunoprecipitation techniques.
KEY RESULTS: The cloned subunits interacted with each other, forming GABA-gated heteromeric channels with particular properties. Strikingly, these heteromers were always more sensitive than AmRDL homomer to all the pharmacological agents tested. In particular, when expressed together, Grd and Lcch3 form a non-selective cationic channel that opens at low concentrations of GABA and with sensitivity to insecticides similar to that of homomeric Rdl channels.
CONCLUSION AND IMPLICATIONS: For off-target species like the honeybee, chronic sublethal exposure to insecticides constitutes a major threat. At these concentration ranges, homomeric RDL receptors may not be the most pertinent target to study and other ionotropic GABA receptor subtypes should be considered in order to understand more fully the molecular mechanisms of sublethal toxicity to insecticides.
Alexander,
THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels.
2019, Pubmed
Alexander,
THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels.
2019,
Pubmed
Aliouane,
Subchronic exposure of honeybees to sublethal doses of pesticides: effects on behavior.
2009,
Pubmed
Aronstein,
Distribution of two GABA receptor-like subunits in the Drosophila CNS.
1996,
Pubmed
Ashby,
GABA binding to an insect GABA receptor: a molecular dynamics and mutagenesis study.
2012,
Pubmed
,
Xenbase
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase
Beg,
EXP-1 is an excitatory GABA-gated cation channel.
2003,
Pubmed
,
Xenbase
Ben-Ari,
GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations.
2007,
Pubmed
Ben-Ari,
Excitatory actions of gaba during development: the nature of the nurture.
2002,
Pubmed
Branicky,
Specification of muscle neurotransmitter sensitivity by a Paired-like homeodomain protein in Caenorhabditis elegans.
2005,
Pubmed
Buckingham,
Insect GABA receptors: splicing, editing, and targeting by antiparasitics and insecticides.
2005,
Pubmed
Carta,
A pentasymmetric open channel blocker for Cys-loop receptor channels.
2014,
Pubmed
Casida,
Novel GABA receptor pesticide targets.
2015,
Pubmed
Casida,
Neuroactive insecticides: targets, selectivity, resistance, and secondary effects.
2013,
Pubmed
Cens,
Characterization of the first honeybee Ca²⁺ channel subunit reveals two novel species- and splicing-specific modes of regulation of channel inactivation.
2013,
Pubmed
,
Xenbase
Charnet,
An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine receptor.
1990,
Pubmed
Charreton,
A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera.
2015,
Pubmed
Comitani,
The Free Energy Landscape of GABA Binding to a Pentameric Ligand-Gated Ion Channel and Its Disruption by Mutations.
2016,
Pubmed
Comitani,
Insights into the binding of GABA to the insect RDL receptor from atomistic simulations: a comparison of models.
2014,
Pubmed
Corringer,
Mutational analysis of the charge selectivity filter of the alpha7 nicotinic acetylcholine receptor.
1999,
Pubmed
,
Xenbase
Cossart,
Operational hub cells: a morpho-physiologically diverse class of GABAergic neurons united by a common function.
2014,
Pubmed
Curtis,
Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers.
2018,
Pubmed
Decourtye,
Comparative sublethal toxicity of nine pesticides on olfactory learning performances of the honeybee Apis mellifera.
2005,
Pubmed
Del Villar,
Cloning and Functional Characterisation of the Duplicated RDL Subunits from the Pea Aphid, Acyrthosiphon pisum.
2018,
Pubmed
,
Xenbase
Dupuis,
Homomeric RDL and heteromeric RDL/LCCH3 GABA receptors in the honeybee antennal lobes: two candidates for inhibitory transmission in olfactory processing.
2010,
Pubmed
Déglise,
The insecticide imidacloprid is a partial agonist of the nicotinic receptor of honeybee Kenyon cells.
2002,
Pubmed
Eguchi,
Functional characterization of Musca glutamate- and GABA-gated chloride channels expressed independently and coexpressed in Xenopus oocytes.
2006,
Pubmed
,
Xenbase
El Hassani,
Effects of sublethal doses of fipronil on the behavior of the honeybee (Apis mellifera).
2005,
Pubmed
Enell,
gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter.
2007,
Pubmed
Ffrench-Constant,
A point mutation in a Drosophila GABA receptor confers insecticide resistance.
1993,
Pubmed
,
Xenbase
Ffrench-Constant,
Ion channels as insecticide targets.
2016,
Pubmed
Ffrench-Constant,
Molecular cloning and transformation of cyclodiene resistance in Drosophila: an invertebrate gamma-aminobutyric acid subtype A receptor locus.
1991,
Pubmed
Galzi,
Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic.
1992,
Pubmed
,
Xenbase
Ganeshina,
GABA-immunoreactive neurons in the mushroom bodies of the honeybee: an electron microscopic study.
2001,
Pubmed
Gisselmann,
Drosophila melanogaster GRD and LCCH3 subunits form heteromultimeric GABA-gated cation channels.
2004,
Pubmed
,
Xenbase
Gou,
Evolution of neurotransmitter gamma-aminobutyric acid, glutamate and their receptors.
2012,
Pubmed
Grutter,
Molecular tuning of fast gating in pentameric ligand-gated ion channels.
2005,
Pubmed
Grünewald,
An ionotropic GABA receptor in cultured mushroom body Kenyon cells of the honeybee and its modulation by intracellular calcium.
2008,
Pubmed
Harding,
The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY.
2018,
Pubmed
Harvey,
Sequence of a Drosophila ligand-gated ion-channel polypeptide with an unusual amino-terminal extracellular domain.
1994,
Pubmed
Henderson,
PCR-based homology probing reveals a family of GABA receptor-like genes in Drosophila melanogaster.
1994,
Pubmed
Henry,
Heterogeneous expression of GABA receptor-like subunits LCCH3 and GRD reveals functional diversity of GABA receptors in the honeybee Apis mellifera.
2020,
Pubmed
,
Xenbase
Holder,
Fipronil pesticide as a suspect in historical mass mortalities of honey bees.
2018,
Pubmed
Hosie,
Molecular biology of insect neuronal GABA receptors.
1997,
Pubmed
Hosie,
Alternative splicing of a Drosophila GABA receptor subunit gene identifies determinants of agonist potency.
2001,
Pubmed
,
Xenbase
Hosie,
Actions of the insecticide fipronil, on dieldrin-sensitive and- resistant GABA receptors of Drosophila melanogaster.
1995,
Pubmed
,
Xenbase
Hosie,
Agonist pharmacology of two Drosophila GABA receptor splice variants.
1996,
Pubmed
,
Xenbase
Houston,
Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors.
2007,
Pubmed
Huang,
Functional integrity of honeybee (Apis mellifera L.) resistant to dieldrin γ-aminobutyric acid receptor channels conjugated with three fluorescent proteins.
2019,
Pubmed
,
Xenbase
Jensen,
The beta subunit determines the ion selectivity of the GABAA receptor.
2002,
Pubmed
Jia,
Identification of the ionotropic GABA receptor-like subunits from the striped stem borer, Chilo suppressalis Walker (Lepidoptera: Pyralidae).
2019,
Pubmed
Jinguji,
Effects of short-term, sublethal fipronil and its metabolite on dragonfly feeding activity.
2018,
Pubmed
Jobson,
Spillover transmission is mediated by the excitatory GABA receptor LGC-35 in C. elegans.
2015,
Pubmed
,
Xenbase
Jones,
Splice-variant- and stage-specific RNA editing of the Drosophila GABA receptor modulates agonist potency.
2009,
Pubmed
,
Xenbase
Kash,
Coupling of agonist binding to channel gating in the GABA(A) receptor.
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,
The activation mechanism of alpha1beta2gamma2S and alpha3beta3gamma2S GABAA receptors.
2010,
Pubmed
Keramidas,
Ligand-gated ion channels: mechanisms underlying ion selectivity.
2004,
Pubmed
Khalilov,
Dynamic Changes from Depolarizing to Hyperpolarizing GABAergic Actions during Giant Depolarizing Potentials in the Neonatal Rat Hippocampus.
2015,
Pubmed
Kilkenny,
Animal research: reporting in vivo experiments: the ARRIVE guidelines.
2010,
Pubmed
Lee,
Calcineurin regulates enteric muscle contraction through EXP-1, excitatory GABA-gated channel, in C. elegans.
2005,
Pubmed
Lema,
Modes and models of GABA(A) receptor gating.
2006,
Pubmed
Liu,
GABAA receptor RDL inhibits Drosophila olfactory associative learning.
2007,
Pubmed
Ludmerer,
Ivermectin and nodulisporic acid receptors in Drosophila melanogaster contain both gamma-aminobutyric acid-gated Rdl and glutamate-gated GluCl alpha chloride channel subunits.
2002,
Pubmed
Lummis,
Locating GABA in GABA receptor binding sites.
2009,
Pubmed
Menard,
Chimeric mutations in the M2 segment of the 5-hydroxytryptamine-gated chloride channel MOD-1 define a minimal determinant of anion/cation permeability.
2005,
Pubmed
,
Xenbase
Ménard,
Multiple combinations of RDL subunits diversify the repertoire of GABA receptors in the honey bee parasite Varroa destructor.
2018,
Pubmed
,
Xenbase
Okada,
Gamma-aminobutyric acid (GABA)-mediated neural connections in the Drosophila antennal lobe.
2009,
Pubmed
Olsen,
GABA A receptors: subtypes provide diversity of function and pharmacology.
2009,
Pubmed
Pisa,
Effects of neonicotinoids and fipronil on non-target invertebrates.
2015,
Pubmed
Rauh,
Pharmacological and biochemical properties of insect GABA receptors.
1990,
Pubmed
Sattelle,
GABA receptors on the cell-body membrane of an identified insect motor neuron.
1988,
Pubmed
Schäfer,
Distribution of GABA-like immunoreactivity in the brain of the honeybee.
1986,
Pubmed
Sieghart,
A novel GABA(A) receptor pharmacology: drugs interacting with the α(+) β(-) interface.
2012,
Pubmed
Sigel,
Structure, function, and modulation of GABA(A) receptors.
2012,
Pubmed
Taylor-Wells,
Cloning and functional expression of intracellular loop variants of the honey bee (Apis mellifera) RDL GABA receptor.
2017,
Pubmed
,
Xenbase
Thompson,
A single ring of charged amino acids at one end of the pore can control ion selectivity in the 5-HT3 receptor.
2003,
Pubmed
Valeeva,
An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons.
2016,
Pubmed
Witte,
Putative histamine-gated chloride channel subunits of the insect visual system and thoracic ganglion.
2002,
Pubmed
Wolff,
Characterization and comparative pharmacological studies of a functional gamma-aminobutyric acid (GABA) receptor cloned from the tobacco budworm, Heliothis virescens (Noctuidae:Lepidoptera).
1998,
Pubmed
,
Xenbase
Wotring,
Mutations at the GABA receptor selectivity filter: a possible role for effective charges.
2003,
Pubmed
,
Xenbase
Zhang,
Subunit composition determines picrotoxin and bicuculline sensitivity of Drosophila gamma-aminobutyric acid receptors.
1995,
Pubmed
,
Xenbase
ffrench-Constant,
Drosophila gamma-aminobutyric acid receptor gene Rdl shows extensive alternative splicing.
1993,
Pubmed
