title: Positive modulation of a Cys-loop acetylcholine receptor by an auxiliary transmembrane subunit.
abstract: Auxiliary subunits regulate the trafficking, localization or gating kinetics of voltage- and ligand-gated ion channels by associating tightly and specifically with pore-forming subunits. However, no auxiliary subunits have been identified for members of the Cys-loop receptor superfamily. Here we identify MOLO-1, a positive regulator of levamisole-sensitive acetylcholine receptors (L-AChRs) at the Caenorhabditis elegans neuromuscular junction. MOLO-1 is a one-pass transmembrane protein that contains a single extracellular globular domain-the TPM domain, found in bacteria, plants and invertebrates, including nonvertebrate chordates. Loss of MOLO-1 impairs locomotion and renders worms resistant to the anthelmintic drug levamisole. In molo-1 mutants, L-AChR-dependent synaptic transmission is reduced by half, while the number and localization of receptors at synapses remain unchanged. In a heterologous expression system, MOLO-1 physically interacts with L-AChRs and directly enhances channel gating without affecting unitary conductance. The identification of MOLO-1 expands the mechanisms for generating functional and pharmacological diversity in the Cys-loop superfamily.
authors.affiliation: Institut de Biologie de l'École Normale Supérieure, Département de Biologie, Paris, France. boulin@biologie.ens.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Boulin
authors.forename: Georgia
authors.initials: G
authors.lastname: Rapti
authors.forename: Luis
authors.initials: L
authors.lastname: Briseño-Roa
authors.forename: Christian
authors.initials: C
authors.lastname: Stigloher
authors.forename: Janet E
authors.initials: JE
authors.lastname: Richmond
authors.forename: Pierre
authors.initials: P
authors.lastname: Paoletti
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bessereau
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D058466:Cysteine Loop Ligand-Gated Ion Channel Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D007978:Levamisole / Q000494:pharmacology; D008124:Locomotion; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009154:Mutation; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D018679:Cholinergic Agonists; D058466:Cysteine Loop Ligand-Gated Ion Channel Receptors; D007473:Ion Channels; D021122:Protein Subunits; D011950:Receptors, Cholinergic; C576761:molo-1 protein, C elegans; D007978:Levamisole