1. Neuroscience
Download icon

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

  1. Nengyin Sheng
  2. Yun S Shi
  3. Richa Madan Lomash
  4. Katherine W Roche
  5. Roger A Nicoll  Is a corresponding author
  1. University of California, San Francisco, United States
  2. National Institutes of Health, United States
Research Article
  • Cited 17
  • Views 1,558
  • Annotations
Cite this article as: eLife 2015;4:e11682 doi: 10.7554/eLife.11682

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.

Article and author information

Author details

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.

Reviewing Editor

  1. Marlene Bartos, Albert-Ludwigs-Universität Freiburg, Germany

Publication history

  1. Received: September 17, 2015
  2. Accepted: December 21, 2015
  3. Accepted Manuscript published: December 31, 2015 (version 1)
  4. Version of Record published: January 30, 2016 (version 2)

Copyright

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.

Metrics

  • 1,558
    Page views
  • 453
    Downloads
  • 17
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    2. Neuroscience
    Ricardo M Santos, Anton Sirota
    Research Article Updated

    Cholinergic fast time-scale modulation of cortical physiology is critical for cognition, but direct local measurement of neuromodulators in vivo is challenging. Choline oxidase (ChOx)-based electrochemical biosensors have been used to capture fast cholinergic signals in behaving animals. However, these transients might be biased by local field potential and O2-evoked enzymatic responses. Using a novel Tetrode-based Amperometric ChOx (TACO) sensor, we performed highly sensitive and selective simultaneous measurement of ChOx activity (COA) and O2. In vitro and in vivo experiments, supported by mathematical modeling, revealed that non-steady-state enzyme responses to O2 give rise to phasic COA dynamics. This mechanism accounts for most of COA transients in the hippocampus, including those following locomotion bouts and sharp-wave/ripples. Our results suggest that it is unfeasible to probe phasic cholinergic signals under most behavioral paradigms with current ChOx biosensors. This confound is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs.

    1. Neuroscience
    Nina Rouhani, Yael Niv
    Research Article

    Memory helps guide behavior, but which experiences from the past are prioritized? Classic models of learning posit that events associated with unpredictable outcomes as well as, paradoxically, predictable outcomes, deploy more attention and learning for those events. Here, we test reinforcement learning and subsequent memory for those events, and treat signed and unsigned reward prediction errors (RPEs), experienced at the reward-predictive cue or reward outcome, as drivers of these two seemingly contradictory signals. By fitting reinforcement learning models to behavior, we find that both RPEs contribute to learning by modulating a dynamically changing learning rate. We further characterize the effects of these RPE signals on memory, and show that both signed and unsigned RPEs enhance memory, in line with midbrain dopamine and locus-coeruleus modulation of hippocampal plasticity, thereby reconciling separate findings in the literature.