通过发动蛋白-3与Homer的物理偶联实现内吞区的突触后定位和AMPA受体循环。
Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer.
作者信息
Lu Jiuyi, Helton Thomas D, Blanpied Thomas A, Rácz Bence, Newpher Thomas M, Weinberg Richard J, Ehlers Michael D
机构信息
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Neuron. 2007 Sep 20;55(6):874-89. doi: 10.1016/j.neuron.2007.06.041.
Abstract
Endocytosis of AMPA receptors and other postsynaptic cargo occurs at endocytic zones (EZs), stably positioned sites of clathrin adjacent to the postsynaptic density (PSD). The tight localization of postsynaptic endocytosis is thought to control spine composition and regulate synaptic transmission. However, the mechanisms that situate the EZ near the PSD and the role of spine endocytosis in synaptic transmission are unknown. Here, we report that a physical link between dynamin-3 and the postsynaptic adaptor Homer positions the EZ near the PSD. Disruption of dynamin-3 or its interaction with Homer uncouples the PSD from the EZ, resulting in synapses lacking postsynaptic clathrin. Loss of the EZ leads to a loss of synaptic AMPA receptors and reduced excitatory synaptic transmission that corresponds with impaired synaptic recycling. Thus, a physical link between the PSD and the EZ ensures localized endocytosis and recycling by recapturing and maintaining a proximate pool of cycling AMPA receptors.
摘要
AMPA 受体及其他突触后货物的内吞作用发生在内吞区（EZs），即网格蛋白在与突触后致密区（PSD）相邻位置稳定存在的位点。突触后内吞作用的紧密定位被认为可控制棘突组成并调节突触传递。然而，将内吞区定位在突触后致密区附近的机制以及棘突内吞作用在突触传递中的作用尚不清楚。在此，我们报告发动蛋白 3 与突触后衔接蛋白 Homer 之间的物理连接将内吞区定位在突触后致密区附近。发动蛋白 3 或其与 Homer 的相互作用被破坏会使突触后致密区与内吞区分离，导致突触缺乏突触后网格蛋白。内吞区的缺失会导致突触 AMPA 受体丢失，并使兴奋性突触传递减少，这与突触循环受损相对应。因此，突触后致密区与内吞区之间的物理连接通过重新捕获并维持循环 AMPA 受体的近端池来确保局部内吞作用和循环利用。
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