The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory

Elife. 2017 Dec 4;6:e24192. doi: 10.7554/eLife.24192.

Abstract

Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs in artificial expression systems, but it is unknown whether Shisa7 has a functional role in glutamatergic synapses. We show that Shisa7 physically interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic expression. Shisa7 KO mice showed reduced initiation and maintenance of long-term potentiation of glutamatergic synapses. In line with this, Shisa7 KO mice showed a specific deficit in contextual fear memory, both short-term and long-term after conditioning, whereas auditory fear memory and anxiety-related behavior were normal. Thus, Shisa7 is a bona-fide AMPAR modulatory protein affecting channel kinetics of AMPARs, necessary for synaptic hippocampal plasticity, and memory recall.

Keywords: Glutamate receptor; Shisa; auxiliary protein; long-term potentiation (LTP); mouse; neuroscience; protein interaction; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Gene Knockout Techniques
  • Hippocampus / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Memory*
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Protein Interaction Mapping
  • Receptors, AMPA / metabolism*
  • Synapses / physiology*

Substances

  • CKAMP59 protein, mouse
  • Carrier Proteins
  • Membrane Proteins
  • Receptors, AMPA

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.