Studniarczyk, D;
Coombs, I;
Cull-Candy, SG;
Farrant, M;
(2013)
TARP γ-7 selectively enhances synaptic expression of calcium-permeable AMPARs.
Nature Neuroscience
, 16
(9)
pp. 1266-1274.
10.1038/nn.3473.
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TARP γ-7 selectively enhances synaptic expression of calcium-permeable AMPARs.pdf - Accepted Version Download (2MB) | Preview |
Abstract
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.
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