Auxiliary subunits of the AMPA receptor: The Shisa family of proteins

Curr Opin Pharmacol. 2021 Jun:58:52-61. doi: 10.1016/j.coph.2021.03.001. Epub 2021 Apr 21.


AMPA receptors mediate fast synaptic transmission in the CNS and can assemble with several types of auxiliary proteins in a spatio-temporal manner, from newly synthesized AMPA receptor tetramers to mature AMPA receptors in the cell membrane. As such, the interaction of auxiliary subunits with the AMPA receptor plays a major role in the regulation of AMPA receptor biogenesis, trafficking, and biophysical properties. Throughout the years, various 'families' of proteins have been identified and today the approximate full complement of AMPAR auxiliary proteins is known. This review presents the current knowledge on the most prominent AMPA-receptor-interacting auxiliary proteins, highlights recent results regarding the Shisa protein family, and provides a discussion on future research that might contribute to the discovery of novel pharmacological targets of auxiliary subunits.

Keywords: Auxiliary proteins; Ionotropic glutamate receptor; Modulation of channel function; Receptor targeting.

Publication types

  • Review

MeSH terms

  • Cell Membrane / metabolism
  • Protein Subunits / metabolism
  • Receptors, AMPA* / metabolism
  • Synaptic Transmission*


  • Protein Subunits
  • Receptors, AMPA