title: The SOL-2/Neto auxiliary protein modulates the function of AMPA-subtype ionotropic glutamate receptors.
abstract: The neurotransmitter glutamate mediates excitatory synaptic transmission by gating ionotropic glutamate receptors (iGluRs). AMPA receptors (AMPARs), a subtype of iGluR, are strongly implicated in synaptic plasticity, learning, and memory. We previously discovered two classes of AMPAR auxiliary proteins in C. elegans that modify receptor kinetics and thus change synaptic transmission. Here, we have identified another auxiliary protein, SOL-2, a CUB-domain protein that associates with both the related auxiliary subunit SOL-1 and with the GLR-1 AMPAR. In sol-2 mutants, behaviors dependent on glutamatergic transmission are disrupted, GLR-1-mediated currents are diminished, and GLR-1 desensitization and pharmacology are modified. Remarkably, a secreted variant of SOL-1 delivered in trans can rescue sol-1 mutants, and this rescue depends on in cis expression of SOL-2. Finally, we demonstrate that SOL-1 and SOL-2 have an ongoing role in the adult nervous system to control AMPAR-mediated currents.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Mellem
authors.forename: Michael
authors.initials: M
authors.lastname: Jensen
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Brockie
authors.forename: Craig S
authors.initials: CS
authors.lastname: Walker
authors.forename: Frédéric J
authors.initials: FJ
authors.lastname: Hoerndli
authors.forename: Linda
authors.initials: L
authors.lastname: Hauth
authors.forename: David M
authors.initials: DM
authors.lastname: Madsen
authors.forename: Andres V
authors.initials: AV
authors.lastname: Maricq
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D026502:LDL-Receptor Related Proteins; D008077:Lipoproteins, LDL / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008969:Molecular Sequence Data; D009865:Oocytes; D017434:Protein Structure, Tertiary / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D029742:Caenorhabditis elegans Proteins; D026502:LDL-Receptor Related Proteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C456602:NETO1 protein, human; C486748:Neto1 protein, mouse; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C576394:SOL-2 protein, C elegans; C096470:glr-1 protein, C elegans