Regulation of AMPA receptors by IgSF11, a PSD-95-interacting synaptic adhesion molecule

Abstract

Glutamate receptors are very important for various neuronal functions including synaptic transmission, learning and memory. However, little is known how synaptic adhesion molecules functionally interact with AMPA receptors (AMPARs). I found that the immunoglobulin superfamily member 11 (IgSF11) as a novel binding partner of the postsynaptic scaffolding protein PSD-95. IgSF11 is enriched at synapses, and PSD-95 promotes synaptic localization of IgSF11. IgSF11 forms a complex with the subunits of AMPA receptors (GluA1 or GluA2). IgSF11 coexpressed with GluA1 in heterologous cells increased the amplitude of GluA1-mediated currents, but had no effect on gating kinetics. In contrast, knockdown of IgSF11 decreased surface expression of GluA1 and GluA2, and synaptic transmission in cultured neurons as well as in organotypic hippocampal slice culture. Knockdown of IgSF11 increased surface mobility of AMPARs, as measured by a new high-throughput single molecule imaging technique. These results suggest that IgSF11 is a novel regulator of synaptic stability of AMPARs interacting with PSD-95.