Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability

Penelope J. Brockie, Michael Jensen, Jerry E. Mellem, Erica Jensen, Tokiwa Yamasaki, Rui Wang, Dane Maxfield, Colin Thacker, Frédéric Hoerndli, Patrick J. Dunn, Susumu Tomita, David M. Madsen, Andres V. Maricq

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 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

Original languageEnglish
Pages (from-to)129-142
Number of pages14
JournalNeuron
Volume80
Issue number1
DOIs
Publication statusPublished - 2013 Oct 2
Externally publishedYes

Fingerprint

AMPA Receptors
Vertebrates
Phenotype
Ionotropic Glutamate Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Invertebrates
Synaptic Transmission
Endoplasmic Reticulum
Synapses
Nervous System
Glutamic Acid
Communication
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Brockie, P. J., Jensen, M., Mellem, J. E., Jensen, E., Yamasaki, T., Wang, R., ... Maricq, A. V. (2013). Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability. Neuron, 80(1), 129-142. https://doi.org/10.1016/j.neuron.2013.07.028

Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability. / Brockie, Penelope J.; Jensen, Michael; Mellem, Jerry E.; Jensen, Erica; Yamasaki, Tokiwa; Wang, Rui; Maxfield, Dane; Thacker, Colin; Hoerndli, Frédéric; Dunn, Patrick J.; Tomita, Susumu; Madsen, David M.; Maricq, Andres V.

In: Neuron, Vol. 80, No. 1, 02.10.2013, p. 129-142.

Research output: Contribution to journalArticle

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 2013, 'Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability', Neuron, vol. 80, no. 1, pp. 129-142. https://doi.org/10.1016/j.neuron.2013.07.028
Brockie, Penelope J. ; Jensen, Michael ; Mellem, Jerry E. ; Jensen, Erica ; Yamasaki, Tokiwa ; Wang, Rui ; Maxfield, Dane ; Thacker, Colin ; Hoerndli, Frédéric ; Dunn, Patrick J. ; Tomita, Susumu ; Madsen, David M. ; Maricq, Andres V. / Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability. In: Neuron. 2013 ; Vol. 80, No. 1. pp. 129-142.
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