A Role for SNAP25 in Internalization of Kainate Receptors and Synaptic Plasticity
A Role for SNAP25 in Internalization of Kainate Receptors and Synaptic Plasticity
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DOI：
10.1016/j.neuron.2009.07.017
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发表时间：
2009-08-13
期刊：
影响因子：
16.2
通讯作者：
Lerma, Juan
中科院分区：
文献类型：
--
作者：
Selak, Sanja;Paternain, Ana V.;Lerma, Juan
AMPA和NMDA受体的表面插入和内化调节已成为控制突触强度的关键机制。然而，突触盐酸盐受体（KARs）的调控元件在很大程度上是不确定的。我们发现SNAP25通过GluK5（即KA2）亚基对KARs的突触移除至关重要。在海马神经元和转染的HEK293细胞中，SNAP25与含有PICK1、GRIP1和GluK5的蛋白复合物共免疫沉淀，并与GluK5共定位。在海马切片中，纯化的SNAP25抗体和阻断肽引起从CA3锥体神经元中记录的kar介导的EPSCKAR （EPSCKAR）的gluk5依赖性上升，并阻止了EPSCKAR活性依赖性的长期抑制。作为EPSCKAR LTD， SNAP25/PICK1/GluK5的相互作用是由PKC动态调控的。
Regulation of surface insertion and internalization of AMPA and NMDA receptors has emerged as a key mechanism for the control of synaptic strength. Regulatory elements for synaptic kainate receptors (KARs) are, however, largely undetermined. We have found that SNAP25 is critical for the synaptic removal of KARs, acting via GluK5 (i.e., KA2) sub-units. SNAP25 coimmunoprecipitates with protein complexes containing PICK1, GRIP1, and GluK5 and colocalizes with GluK5 in both hippocampal neurons and transfected HEK293 cells. In hippocampal slices, purified SNAP25 antibodies and blocking peptides caused a GluK5-dependent run-up of KARs-mediated EPSC (EPSCKAR) recorded from CA3 pyramidal neurons when included in the patch pipette and prevented activity-dependent long-term depression of EPSCKAR. As EPSCKAR LTD, SNAP25/PICK1/GluK5 interactions are dynamically regulated by PKC.