title: GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons.
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.
authors.affiliation: 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.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Xia
authors.initials: X
authors.lastname: Mao
authors.affiliation: Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 2C903, Bethesda, Maryland 20892, USA.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Lussier
authors.affiliation: 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.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Hutchison
authors.affiliation: 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.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Cecil H. &Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center in Dallas, Dallas, Texas 75390, USA.
authors.forename: F Kent
authors.initials: FK
authors.lastname: Hamra
authors.affiliation: Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 2C903, Bethesda, Maryland 20892, USA.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Roche
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D010957:Plasmids; D021122:Protein Subunits; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D008565:Membrane Proteins
chemical_list: D057167:Claudins; D021122:Protein Subunits; D018091:Receptors, AMPA; C578454:GSG1L protein, rat; D008565:Membrane Proteins