Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5

Nat Neurosci. 2009 Mar;12(3):277-85. doi: 10.1038/nn.2266. Epub 2009 Feb 22.


Although the properties and trafficking of AMPA-type glutamate receptors (AMPARs) depend critically on associated transmembrane AMPAR regulatory proteins (TARPs) such as stargazin (gamma-2), no TARP has been described that can specifically regulate the important class of calcium-permeable (CP-) AMPARs. We examined the stargazin-related protein gamma-5, which is highly expressed in Bergmann glia, a cell type possessing only CP-AMPARs. gamma-5 was previously thought not to be a TARP, and it has been widely used as a negative control. Here we find that, contrary to expectation, gamma-5 acts as a TARP and serves this role in Bergmann glia. Whereas gamma-5 interacts with all AMPAR subunits, and modifies their behavior to varying extents, its main effect is to regulate the function of AMPAR subunit combinations that lack short-form subunits, which constitute predominantly CP-AMPARs. Our results suggest an important role for gamma-5 in regulating the functional contribution of CP-AMPARs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / physiology
  • Calcium Signaling / genetics
  • Calcium Signaling / physiology*
  • Cell Line
  • Cell Membrane Permeability / genetics
  • Cell Membrane Permeability / physiology*
  • Humans
  • Neuroglia / chemistry
  • Neuroglia / metabolism
  • Neuroglia / physiology
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Protein Transport / genetics
  • Rats
  • Receptors, AMPA / classification*
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology*


  • Cacng2 protein, rat
  • Cacng5 protein, rat
  • Calcium Channels
  • Protein Isoforms
  • Receptors, AMPA
  • Calcium