A novel action of stargazin as an enhancer of AMPA receptor activity

Neurosci Res. 2004 Dec;50(4):369-74. doi: 10.1016/j.neures.2004.10.002.


Stargazin (gamma-2) is disrupted in the ataxic and epileptic mutant mouse, stargazer (stg). The striking defect in the stg cerebellum is the lack of functional AMPA receptors on granule cells. Recently, it has been reported that gamma-2 and its related molecules are crucial for the surface expression, synaptic targeting and recycling of AMPA receptors, being termed collectively as the transmembrane AMPA receptor regulatory proteins (TARPs). However, it is still unclear whether TARPs directly modulate AMPA receptor activity. Here we report that coexpression of GluRalpha1 (GluR1) with gamma-2 using HEK293 cells and Xenopus oocytes markedly enhanced glutamate-induced currents. This effect was far beyond the increase of AMPA receptor surface expression and accompanied by increased glutamate affinity and subunit cooperativity. Other member of TARPs (gamma-3, gamma-4, and gamma-8) also enhanced the current response through the AMPA receptors. The enhancing effect by gamma-2 coexpression was further observed for homomeric GluRalpha2 (GluR2) channels, which, when expressed alone, are known to produce only a small or negligible current response. These results suggest that gamma-2 not only promotes AMPA receptor surface expression but also directly modulates AMPA receptor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / genetics
  • Cell Membrane / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation / genetics
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Humans
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Neurons / metabolism*
  • Oocytes
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport / genetics
  • Receptor Aggregation / genetics
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Xenopus laevis


  • CACNG2 protein, human
  • Calcium Channels
  • Protein Subunits
  • Receptors, AMPA
  • Glutamic Acid
  • glutamate receptor ionotropic, AMPA 2
  • glutamate receptor ionotropic, AMPA 1