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

Xinglong Gu; Xia Mao; Marc P. Lussier; Mary Anne Hutchison; Liang Zhou; F. Kent Hamra; Katherine W. Roche; Wei Lu

doi:10.1038/ncomms10873

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

Xinglong Gu, Xia Mao, Marc P. Lussier, Mary Anne Hutchison, Liang Zhou, F. Kent Hamra, Katherine W. Roche, Wei Lu

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Article number	10873
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10873
State	Published - Mar 2 2016

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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.",

author = "Xinglong Gu and Xia Mao and Lussier, {Marc P.} and Hutchison, {Mary Anne} and Liang Zhou and Hamra, {F. Kent} and Roche, {Katherine W.} and Wei Lu",

note = "Funding Information: We thank Dr Tianyi Wang at the University of Pittsburgh for the Claudin1 plasmid. We also appreciate Dr Bernd Fakler at the University of Freiburg, Germany for sharing the GSG1L data from his lab with us. We are grateful to Drs Jeffrey Diamond and Mark Mayer for critical comments on the manuscript. This work was supported by the NINDS Intramural Research Program (W.L. and K.W.R.). Gsg1l mutant rats were produced by the NIH Mutant Rat Resource at UT Southwestern Medical Center in Dallas under grants from the National Center for Research Resources, R24RR03232601 and the Office of the Director, R24OD011108 to F.K.H.",

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T1 - GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons

AU - Gu, Xinglong

AU - Mao, Xia

AU - Lussier, Marc P.

AU - Hutchison, Mary Anne

AU - Zhou, Liang

AU - Hamra, F. Kent

AU - Roche, Katherine W.

AU - Lu, Wei

N1 - Funding Information: We thank Dr Tianyi Wang at the University of Pittsburgh for the Claudin1 plasmid. We also appreciate Dr Bernd Fakler at the University of Freiburg, Germany for sharing the GSG1L data from his lab with us. We are grateful to Drs Jeffrey Diamond and Mark Mayer for critical comments on the manuscript. This work was supported by the NINDS Intramural Research Program (W.L. and K.W.R.). Gsg1l mutant rats were produced by the NIH Mutant Rat Resource at UT Southwestern Medical Center in Dallas under grants from the National Center for Research Resources, R24RR03232601 and the Office of the Director, R24OD011108 to F.K.H.

PY - 2016/3/2

Y1 - 2016/3/2

N2 - 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.

AB - 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.

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

Abstract

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