TARP γ-7 selectively enhances synaptic expression of calcium-permeable AMPARs

Nat Neurosci. 2013 Sep;16(9):1266-74. doi: 10.1038/nn.3473. Epub 2013 Jul 21.


Regulation of calcium-permeable AMPA receptors (CP-AMPARs) is crucial in normal synaptic function and neurological disease states. Although transmembrane AMPAR regulatory proteins (TARPs) such as stargazin (γ-2) modulate the properties of calcium-impermeable AMPARs (CI-AMPARs) and promote their synaptic targeting, the TARP-specific rules governing CP-AMPAR synaptic trafficking remain unclear. We used RNA interference to manipulate AMPAR-subunit and TARP expression in γ-2-lacking stargazer cerebellar granule cells--the classic model of TARP deficiency. We found that TARP γ-7 selectively enhanced the synaptic expression of CP-AMPARs and suppressed CI-AMPARs, identifying a pivotal role of γ-7 in regulating the prevalence of CP-AMPARs. In the absence of associated TARPs, both CP-AMPARs and CI-AMPARs were able to localize to synapses and mediate transmission, although their properties were altered. Our results also establish that TARPed synaptic receptors in granule cells require both γ-2 and γ-7 and reveal an unexpected basis for the loss of AMPAR-mediated transmission in stargazer mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Cells, Cultured
  • Cerebellum / cytology
  • Chlorides / metabolism
  • Excitatory Amino Acid Agents / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Female
  • Gene Expression Regulation / genetics*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Neurons / drug effects
  • Neurons / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Spermine / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Chlorides
  • Excitatory Amino Acid Agents
  • Membrane Proteins
  • RNA, Small Interfering
  • Receptors, AMPA
  • TARP gamma-7 protein, mouse
  • Spermine
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • glutamate receptor ionotropic, AMPA 2
  • Calcium