First Author | Studniarczyk D | Year | 2013 |
Journal | Nat Neurosci | Volume | 16 |
Issue | 9 | Pages | 1266-74 |
PubMed ID | 23872597 | Mgi Jnum | J:203892 |
Mgi Id | MGI:5528969 | Doi | 10.1038/nn.3473 |
Citation | Studniarczyk D, et al. (2013) TARP gamma-7 selectively enhances synaptic expression of calcium-permeable AMPARs. Nat Neurosci 16(9):1266-74 |
abstractText | 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 (gamma-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 gamma-2-lacking stargazer cerebellar granule cells--the classic model of TARP deficiency. We found that TARP gamma-7 selectively enhanced the synaptic expression of CP-AMPARs and suppressed CI-AMPARs, identifying a pivotal role of gamma-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 gamma-2 and gamma-7 and reveal an unexpected basis for the loss of AMPAR-mediated transmission in stargazer mice. |