Dynamin-dependent Membrane Drift Recruits AMPA Receptors to Dendritic Spines
Dynamin-dependent Membrane Drift Recruits AMPA Receptors to Dendritic Spines
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DOI：
10.1074/jbc.m808401200
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Henley, Jeremy M.
中科院分区：
文献类型：
--
作者：
Jaskolski, Frederic;Mayo-Martin, Belen;Henley, Jeremy M.
AMPA受体(AMPAR)在树突棘的表面表达和定位受到严格控制，以调节突触传递。在这里，我们证明了GluR2 AMPAR亚单位的从头胞吐发生在树突干上，新的AMPAR通过膜中的横向扩散扩散到棘中。然而，膜的拓扑结构限制了这种横向扩散。因此，我们研究了哪些机制将AMPAR从茎向脊椎招募，并证明了抑制Dynamin GTPase活性减少了膜锚定的绿色荧光蛋白和超黄道PHluorin(SEP)-GluR2向脊椎的侧向扩散。此外，突触N-甲基-D-天冬氨酸(NMDA)受体的激活促进了SEP-GluR2的侧向扩散，并增加了脊髓内源性AMPAR的数量。NMDA激活的效应被动力蛋白抑制所阻止，这表明脊椎内依赖活性的动力蛋白介导的内吞作用产生了净向内的膜漂移，超越了横向扩散障碍，从而增强了膜蛋白向脊椎的输送。这些结果为AMPAR和其他膜蛋白如何通过突触活动被招募到脊柱提供了一种新的机制解释。
The surface expression and localization of AMPA receptors (AMPARs) at dendritic spines are tightly controlled to regulate synaptic transmission. Here we show that de novo exocytosis of the GluR2 AMPAR subunit occurs at the dendritic shaft and that new AMPARs diffuse into spines by lateral diffusion in the membrane. However, membrane topology restricts this lateral diffusion. We therefore investigated which mechanisms recruit AMPARs to spines from the shaft and demonstrated that inhibition of dynamin GTPase activity reduced lateral diffusion of membrane-anchored green fluorescent protein and super-ecliptic pHluorin (SEP)-GluR2 into spines. In addition, the activation of synaptic N-methyl-D-aspartate (NMDA) receptors enhanced lateral diffusion of SEP-GluR2 and increased the number of endogenous AMPARs in spines. The NMDA-invoked effects were prevented by dynamin inhibition, suggesting that activity-dependent dynamin-mediated endocytosis within spines generates a net inward membrane drift that overrides lateral diffusion barriers to enhance membrane protein delivery into spines. These results provide a novel mechanistic explanation of how AMPARs and other membrane proteins are recruited to spines by synaptic activity.