Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity.
Nat Comms. 2016-03-02; 7: 10682
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1. Nat Commun. 2016 Mar 2;7:10682. doi: 10.1038/ncomms10682.
Shisa6 traps AMPA receptors at postsynaptic sites and prevents their
desensitization during synaptic activity.
Klaassen RV(1), Stroeder J(1)(2), Coussen F(3)(4), Hafner AS(3)(4), Petersen
JD(3)(4), Renancio C(3)(4), Schmitz LJ(1), Normand E(3)(4), Lodder JC(2), Rotaru
DC(2), Rao-Ruiz P(1), Spijker S(1), Mansvelder HD(2), Choquet D(3)(4), Smit
(1)Department Molecular and Cellular Neurobiology, 1081 HV Amsterdam, The
(2)Department Integrative Neurophysiology, Center for Neurogenomics and Cognitive
Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, 1081
HV Amsterdam, The Netherlands.
(3)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, F-33000 Bordeaux, France.
(4)CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000
Trafficking and biophysical properties of AMPA receptors (AMPARs) in the brain
depend on interactions with associated proteins. We identify Shisa6, a single
transmembrane protein, as a stable and directly interacting bona fide AMPAR
auxiliary subunit. Shisa6 is enriched at hippocampal postsynaptic membranes and
co-localizes with AMPARs. The Shisa6 C-terminus harbours a PDZ domain ligand that
binds to PSD-95, constraining mobility of AMPARs in the plasma membrane and
confining them to postsynaptic densities. Shisa6 expressed in HEK293 cells alters
GluA1- and GluA2-mediated currents by prolonging decay times and decreasing the
extent of AMPAR desensitization, while slowing the rate of recovery from
desensitization. Using gene deletion, we show that Shisa6 increases rise and
decay times of hippocampal CA1 miniature excitatory postsynaptic currents
(mEPSCs). Shisa6-containing AMPARs show prominent sustained currents, indicating
protection from full desensitization. Accordingly, Shisa6 prevents synaptically
trapped AMPARs from depression at high-frequency synaptic transmission.
PMID: 26931375 [Indexed for MEDLINE]