Tomita Susumu, Shenoy Archana, Fukata Yuko, Nicoll Roger A, Bredt David S
Department of Physiology, University of California at San Francisco, San Francisco, CA 94143, USA.
Neuropharmacology. 2007 Jan;52(1):87-91. doi: 10.1016/j.neuropharm.2006.07.012. Epub 2006 Aug 21.
Neuronal AMPA receptors comprise pore forming glutamate receptor (GluR) proteins and auxiliary transmembrane AMPA receptor regulatory (TARP) subunits. TARPs traffic AMPA receptors to synapses and regulate channel gating. Both intracellular and extracellular regions in TARPs regulate AMPA receptors; however, the details for these interactions remain unknown. Here, we employ site-directed mutagenesis to determine functional interactions between GluR1 and the prototypical TARP, stargazin. We find that a point mutation in the glutamate-binding region of GluR1 corresponding to the Lurcher allele of GluRdelta2, abolishes stargazin's effects on receptor trafficking and channel gating. A point mutation that prevents receptor desensitization modulates the effects of stargazin on channel gating but preserves receptor trafficking. These studies identify a functional interaction of stargazin with the extracellular glutamate-binding domain of AMPA receptors.
神经元α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体由形成孔道的谷氨酸受体（GluR）蛋白和辅助跨膜AMPA受体调节（TARP）亚基组成。TARPs将AMPA受体转运至突触并调节通道门控。TARPs的细胞内和细胞外区域均调节AMPA受体；然而，这些相互作用的细节仍不清楚。在此，我们采用定点突变来确定GluR1与典型TARP——stargazin之间的功能相互作用。我们发现，GluR1谷氨酸结合区域中对应于GluRδ2的Lurcher等位基因的一个点突变，消除了stargazin对受体转运和通道门控的影响。一个阻止受体脱敏的点突变调节了stargazin对通道门控的作用，但保留了受体转运。这些研究确定了stargazin与AMPA受体细胞外谷氨酸结合结构域之间的功能相互作用。
