1. Neuroscience
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Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses

  1. Quynh-Anh Nguyen
  2. Meryl E Horn
  3. Roger A Nicoll  Is a corresponding author
  1. University of California, San Francisco, United States
  2. University of California, San Francisco, United States
Research Article
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Cite this article as: eLife 2016;5:e19236 doi: 10.7554/eLife.19236


Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depends on the presence of NLGN2 and identified a domain in the extracellular region that accounted for this functional difference between NLGN2 and 3 specifically at inhibitory synapses. We further show that the presence of a cytoplasmic tail (c-tail) is indispensible, and identified two domains in the c-tail that are necessary for NLGN function at inhibitory synapses. These domains point to a gephyrin-dependent mechanism that is disrupted by an autism-associated mutation at R705 and a gephyrin-independent mechanism reliant on a putative phosphorylation site at S714. Our work highlights unique and separate roles for the extracellular and intracellular regions in specifying and carrying out NLGN function respectively.

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Author details

  1. Quynh-Anh Nguyen

    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.
  2. Meryl E Horn

    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. Roger A Nicoll

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6977-4632


American Heart Association (Predoctoral Fellowship)

  • Quynh-Anh Nguyen

National Science Foundation (Graduate Research Fellowship)

  • Meryl E Horn

National Institute of Mental Health

  • Roger A Nicoll

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


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 experiments were performed in accordance with established protocols approved by the University of California San Francisco Institutional Animal Care and Use Committee (PHS Assurance #A3400-01).

Reviewing Editor

  1. Eunjoon Kim, Korea Advanced Institute of Science and Technology, Republic of Korea

Publication history

  1. Received: June 29, 2016
  2. Accepted: November 1, 2016
  3. Accepted Manuscript published: November 2, 2016 (version 1)
  4. Version of Record published: November 7, 2016 (version 2)


© 2016, Nguyen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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