The interaction between stargazin and PSD-95 regulates AMPA receptor surface trafficking
The interaction between stargazin and PSD-95 regulates AMPA receptor surface trafficking
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DOI：
10.1016/j.neuron.2007.01.030
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发表时间：
2007-03-01
期刊：
影响因子：
16.2
通讯作者：
Choquet, Daniel
中科院分区：
文献类型：
--
作者：
Bats, Cecile;Groc, Laurent;Choquet, Daniel
AMPA受体在突触上的积累是谷氨酸能突触传递的一个基本特征。Stargazin是TARP家族的一员，是一种AMPAR辅助亚基，允许受体与突触后密度的支架蛋白（如PSD-95）相互作用。PSD-95和Stargazin如何调节突触膜上AMPAR的数量尚不清楚。通过对活海马神经元的单量子点和FRAP成像，我们发现AMPAR通过突触外和突触位点之间的横向扩散交换主要取决于Stargazin与PSD-95的相互作用，而不是GluR2 AMPAR亚基C端。破坏Stargazin和PSD-95之间的相互作用会强烈增加AMPAR的表面扩散，阻止AMPAR在突触后位点的积累。此外，AMPARs和Stargazin作为复合物在突触内外扩散。这些结果提出了一个模型，其中StargazinPSD-95相互作用在突触后密度中捕获和短暂稳定扩散的ampar中起关键作用。
Accumulation of AMPA receptors at synapses is a fundamental feature of glutamatergic synaptic transmission. Stargazin, a member of the TARP family, is an AMPAR auxiliary subunit allowing interaction of the receptor with scaffold proteins of the postsynaptic density, such as PSD-95. How PSD-95 and Stargazin regulate AMPAR number in synaptic membranes remains elusive. We show, using single quantum dot and FRAP imaging in live hippocampal neurons, that exchange of AMPAR by lateral diffusion between extrasynaptic and synaptic sites mostly depends on the interaction of Stargazin with PSD-95 and not upon the GluR2 AMPAR subunit C terminus. Disruption of interactions between Stargazin and PSD-95 strongly increases AMPAR surface diffusion, preventing AMPAR accumulation at postsynaptic sites. Furthermore, AMPARs and Stargazin diffuse as complexes in and out synapses. These results propose a model in which the StargazinPSD-95 interaction plays a key role to trap and transiently stabilize diffusing AMPARs in the postsynaptic density.