Neto auxiliary proteins control both the trafficking and biophysical properties of the kainate receptor GluK1

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Abstract

Kainate receptors (KARs) are a subfamily of glutamate receptors mediating excitatory synaptic transmission and Neto proteins are recently identified auxiliary subunits for KARs. However, the roles of Neto proteins in the synaptic trafficking of KAR GluK1 are poorly understood. Here, using the hippocampal CA1 pyramidal neuron as a null background system we find that surface expression of GluK1 receptor itself is very limited and is not targeted to excitatory synapses. Both Neto1 and Neto2 profoundly increase GluK1 surface expression and also drive GluK1 to synapses. However, the regulation GluK1 synaptic targeting by Neto proteins is independent of their role in promoting surface trafficking. Interestingly, GluK1 is excluded from synapses expressing AMPA receptors and is selectively incorporated into silent synapses. Neto2, but not Neto1, slows GluK1 deactivation, whereas Neto1 speeds GluK1 desensitization and Neto2 slows desensitization. These results establish critical roles for Neto auxiliary subunits controlling KARs properties and synaptic incorporation.

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Nengyin Sheng

Deparment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Yun S Shi

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Richa Madan Lomash

Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Katherine W Roche

Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Roger A Nicoll

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States

For correspondence
roger.nicoll@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were housed in rodent housing at the UCSF and the animal health was monitored by a staff that includes the attending veterinarian, a veterinary pathologist, and a team of veterinary nurses. The University of California, San Francisco has on file with the Office of Protection from Research Risks, National Institutes of Health, U.S. Public Health Service (PHS), an approved Assurance of Compliance with PHS Policy on Humane Care and Use of Laboratory Animals by Awardee Institutions (#3400-01). That document expresses UCSF's commitment to comply with PHS policy and all applicable laws and regulations regarding the care and use of laboratory animals in research and instruction.

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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.