TY - JOUR
T1 - Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability
AU - Brockie, Penelope J.
AU - Jensen, Michael
AU - Mellem, Jerry E.
AU - Jensen, Erica
AU - Yamasaki, Tokiwa
AU - Wang, Rui
AU - Maxfield, Dane
AU - Thacker, Colin
AU - Hoerndli, Frédéric
AU - Dunn, Patrick J.
AU - Tomita, Susumu
AU - Madsen, David M.
AU - Maricq, Andres V.
N1 - Funding Information:
We thank members of the Maricq laboratory and Marcus Babst for comments on the manuscript, Craig Walker for the preliminary analysis of cni-1 mutants and Aleksander Maricq for assistance writing the MATLAB script. Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This research was made possible by support from NIH Grants NS35812 (A.V.M.) and MH077939 (S.T.). T.Y. is supported by the Program for Young Researcher Overseas Visits, Graduate School of Pharmaceutical Science, The University of Tokyo.
PY - 2013/10/2
Y1 - 2013/10/2
N2 - 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 invivo 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
AB - 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 invivo 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
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U2 - 10.1016/j.neuron.2013.07.028
DO - 10.1016/j.neuron.2013.07.028
M3 - Article
C2 - 24094107
AN - SCOPUS:84884757070
SN - 0896-6273
VL - 80
SP - 129
EP - 142
JO - Neuron
JF - Neuron
IS - 1
ER -