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GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons

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  • Xinglong Gu

    (Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, Maryland 20892, USA)

  • Xia Mao

    (Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, Maryland 20892, USA)

  • Marc P. Lussier

    (Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 2C903, Bethesda, Maryland 20892, USA
    Present address: Département de Chimie, Université du Québec à Montréal, Montréal, Québec, Canada H3C 3P8)

  • Mary Anne Hutchison

    (Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, Maryland 20892, USA)

  • Liang Zhou

    (Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, Maryland 20892, USA)

  • F. Kent Hamra

    (Cecil H. & Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center in Dallas)

  • Katherine W. Roche

    (Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 2C903, Bethesda, Maryland 20892, USA)

  • Wei Lu

    (Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, Maryland 20892, USA)

Abstract

Regulation of AMPA receptor (AMPAR)-mediated synaptic transmission is a key mechanism for synaptic plasticity. In the brain, AMPARs assemble with a number of auxiliary subunits, including TARPs, CNIHs and CKAMP44, which are important for AMPAR forward trafficking to synapses. Here we report that the membrane protein GSG1L negatively regulates AMPAR-mediated synaptic transmission. Overexpression of GSG1L strongly suppresses, and GSG1L knockout (KO) enhances, AMPAR-mediated synaptic transmission. GSG1L-dependent regulation of AMPAR synaptic transmission relies on the first extracellular loop domain and its carboxyl-terminus. GSG1L also speeds up AMPAR deactivation and desensitization in hippocampal CA1 neurons, in contrast to the effects of TARPs and CNIHs. Furthermore, GSG1L association with AMPARs inhibits CNIH2-induced slowing of the receptors in heterologous cells. Finally, GSG1L KO rats have deficits in LTP and show behavioural abnormalities in object recognition tests. These data demonstrate that GSG1L represents a new class of auxiliary subunit with distinct functional properties for AMPARs.

Suggested Citation

  • Xinglong Gu & Xia Mao & Marc P. Lussier & Mary Anne Hutchison & Liang Zhou & F. Kent Hamra & Katherine W. Roche & Wei Lu, 2016. "GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons," Nature Communications, Nature, vol. 7(1), pages 1-18, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10873
    DOI: 10.1038/ncomms10873
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    Cited by:

    1. Caleigh M Azumaya & Emily L Days & Paige N Vinson & Shaun Stauffer & Gary Sulikowski & C David Weaver & Terunaga Nakagawa, 2017. "Screening for AMPA receptor auxiliary subunit specific modulators," PLOS ONE, Public Library of Science, vol. 12(3), pages 1-23, March.
    2. Amanda M. Perozzo & Jochen Schwenk & Aichurok Kamalova & Terunaga Nakagawa & Bernd Fakler & Derek Bowie, 2023. "GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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