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 journalArticle

21 Citations (Scopus)

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 languageEnglish (US)
Article number10873
JournalNature Communications
Volume7
DOIs
StatePublished - Mar 2 2016

Fingerprint

AMPA Receptors
neurons
Synaptic Transmission
Neurons
Kinetics
kinetics
Neuronal Plasticity
synapses
Object recognition
Synapses
abnormalities
Plasticity
Rats
Brain
plastic properties
Membrane Proteins
deactivation
rats
brain
membranes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons. / Gu, Xinglong; Mao, Xia; Lussier, Marc P.; Hutchison, Mary Anne; Zhou, Liang; Hamra, F. Kent; Roche, Katherine W.; Lu, Wei.

In: Nature Communications, Vol. 7, 10873, 02.03.2016.

Research output: Contribution to journalArticle

Gu, Xinglong ; Mao, Xia ; Lussier, Marc P. ; Hutchison, Mary Anne ; Zhou, Liang ; Hamra, F. Kent ; Roche, Katherine W. ; Lu, Wei. / GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons. In: Nature Communications. 2016 ; Vol. 7.
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