RRC ID 45933
Author Brockie PJ, Jensen M, Mellem JE, Jensen E, Yamasaki T, Wang R, Maxfield D, Thacker C, Hoerndli F, Dunn PJ, Tomita S, Madsen DM, Maricq AV.
Title Cornichons control ER export of AMPA receptors to regulate synaptic excitability.
Journal Neuron
Abstract The strength of synaptic communication at central synapses depends on the number of ionotropic glutamate receptors, particularly the class gated by the agonist AMPA (AMPARs). Cornichon proteins, evolutionarily conserved endoplasmic reticulum cargo adaptors, modify the properties of vertebrate AMPARs when coexpressed in heterologous cells. However, the contribution of cornichons to behavior and in vivo nervous system function has yet to be determined. Here, we take a genetic approach to these questions by studying CNI-1--the sole cornichon homolog in C. elegans. cni-1 mutants hyperreverse, a phenotype associated with increased glutamatergic synaptic transmission. Consistent with this behavior, we find larger glutamate-gated currents in cni-1 mutants with a corresponding increase in AMPAR number. Furthermore, we observe opposite phenotypes in transgenic worms that overexpress CNI-1 or vertebrate homologs. In reconstitution studies, we provide support for an evolutionarily conserved role for cornichons in regulating the export of vertebrate and invertebrate AMPARs.
Volume 80(1)
Pages 129-42
Published 2013-10-2
DOI 10.1016/j.neuron.2013.07.028
PII S0896-6273(13)00652-1
PMID 24094107
PMC PMC3795439
MeSH Animals Caenorhabditis elegans / metabolism* Cells, Cultured Endoplasmic Reticulum / metabolism* Glutamic Acid / metabolism Membrane Proteins / metabolism* Mutation / genetics Neurons / cytology Neurons / metabolism Protein Transport / physiology Receptors, AMPA / agonists Receptors, AMPA / genetics Receptors, AMPA / metabolism* Synapses / metabolism* Synaptic Transmission / physiology* alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism
IF 14.415
Times Cited 28
WOS Category NEUROSCIENCES
Resource
C.elegans tm4274