The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the βPIX guanine nucleotide exchange factor for Rac1 and Cdc42
The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the βPIX guanine nucleotide exchange factor for Rac1 and Cdc42
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DOI：
10.1074/jbc.m301052200
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发表时间：
2003-05-23
影响因子：
4.8
通讯作者：
Kim, E
中科院分区：
文献类型：
--
作者：
Park, E;Na, M;Kim, E
已知Shank/ProSAP多结构域蛋白家族在组织突触多蛋白复合物中发挥重要作用。在这里，我们报告了一种新的柄和betaPIX，鸟嘌呤核苷酸交换因子的Rac 1和Cdc 42小GTP酶之间的相互作用。这种相互作用由Shank的PDZ结构域和betaPIX的C末端亮氨酸拉链结构域以及末端C末端的PDZ结构域结合基序介导。在培养的神经元中，Shank与betaPIX共定位于兴奋性突触位点。在大脑中，Shank与betaPIX和betaPIX相关信号分子形成复合物，包括P21相关激酶（PAK），Rac 1/Cdc 42的效应激酶。重要的是，在培养的神经元中Shank的过表达促进β PIX和PAK的突触积累。考虑到Rac 1和PAK参与脊柱动力学，这些结果表明，Shank招募betaPIX和PAK的突触后结构的调节脊柱。
The Shank/ProSAP family of multidomain proteins is known to play an important role in organizing synaptic multiprotein complexes. Here we report a novel interaction between Shank and betaPIX, a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases. This interaction is mediated by the PDZ domain of Shank and the C-terminal leucine zipper domain and the PDZ domain-binding motif at the extreme C terminus of betaPIX. Shank colocalizes with betaPIX at excitatory synaptic sites in cultured neurons. In brain, Shank forms a complex with betaPIX and betaPIX-associated signaling molecules including p21-associated kinase (PAK), an effector kinase of Rac1/Cdc42. Importantly, overexpression of Shank in cultured neurons promotes synaptic accumulation of betaPIX and PAK. Considering the involvement of Rac1 and PAK in spine dynamics, these results suggest that Shank recruits betaPIX and PAK to spines for the regulation of postsynaptic structure.