PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking
PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking
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DOI：
10.1016/j.neuron.2005.07.006
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发表时间：
2005-08-04
期刊：
影响因子：
16.2
通讯作者：
Ziff, EB
中科院分区：
文献类型：
--
作者：
Lu, W;Ziff, EB
PICK 1和ABP/GRIP与AMPA受体（AMPAR）GluR 2亚基C末端结合。GluR 2 S880磷酸化促进受体从ABP/GRIP转移到PICK 1，可能启动受体运输。在这里，我们报告蛋白质的相互作用，调节这些步骤。PICK 1 BAR结构域与ABP/GRIP接头11区域分子间相互作用，并与PICK 1 PDZ结构域分子内相互作用。PKC α或GluR 2与PICK 1 PDZ结构域的结合破坏了分子内相互作用，并促进了PICK 1 BAR结构域与ABP/GRIP的结合。干扰PICK 1-ABP/GRIP相互作用会损害PKC对GluR 2的S880磷酸化，并降低GluR 2的组成性表面表达、NMDA诱导的GluR 2内吞作用和内化GluR 2的再循环。我们认为PICK 1与ABP/GRIP的相互作用是控制GluR 2运输的关键步骤。
PICK1 and ABP/GRIP bind to the AMPA receptor (AMPAR) GluR2 subunit C terminus. Transfer of the receptor from ABP/GRIP to PICK1, facilitated by GluR2 S880 phosphorylation, may initiate receptor trafficking. Here we report protein interactions that regulate these steps. The PICK1 BAR domain interacts intermolecularly with the ABP/GRIP linker 11 region and intramolecularly with the PICK1 PDZ domain. Binding of PKC alpha or GluR2 to the PICK1 PDZ domain disrupts the intramolecular interaction and facilitates the PICK1 BAR domain association with ABP/GRIP. Interference with the PICK1-ABP/GRIP interaction impairs S880 phosphorylation of GluR2 by PKC and decreases the constitutive surface expression of GluR2, the NMDA-induced endocytosis of GluR2, and recycling of internalized GluR2. We suggest that the PICK1 interaction with ABP/GRIP is a critical step in controlling GluR2 trafficking.