Bats Cecile, Groc Laurent, Choquet Daniel
Physiologie Cellulaire de la Synapse, UMR 5091 CNRS - Institut François Magendie, Université Bordeaux, Bordeaux 33077, France.
Neuron. 2007 Mar 1;53(5):719-34. doi: 10.1016/j.neuron.2007.01.030.
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 Stargazin-PSD-95 interaction plays a key role to trap and transiently stabilize diffusing AMPARs in the postsynaptic density.
AMPA受体在突触处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AMPA受体辅助亚基，可使该受体与突触后致密物的支架蛋白（如PSD-95）相互作用。PSD-95和Stargazin如何调节突触膜中AMPA受体的数量仍不清楚。我们利用活海马神经元中的单量子点和荧光漂白恢复成像技术表明，AMPA受体通过在突触外和突触部位之间的侧向扩散进行交换，这主要取决于Stargazin与PSD-95的相互作用，而不是GluR2 AMPA受体亚基的C末端。破坏Stargazin与PSD-95之间的相互作用会强烈增加AMPA受体的表面扩散，阻止AMPA受体在突触后部位的积累。此外，AMPA受体和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Stargazin-PSD-95相互作用在捕获和短暂稳定突触后致密物中扩散的AMPA受体方面起着关键作用。
