PICK1 links AMPA receptor stimulation to Cdc42.
PICK1 links AMPA receptor stimulation to Cdc42.
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DOI：
10.1016/j.neulet.2014.11.046
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发表时间：
2015-01-12
影响因子：
2.5
通讯作者：
Hanley JG
中科院分区：
文献类型：
--
作者：
Rocca DL;Hanley JG
PICK 1结合Rac 1和Cdc 42。AMPA受体可以通过PICK 1与Cdc 42相互作用。AMPA刺激以PICK 1依赖性方式增加Cdc 42去污剂溶解度。Rho家族GTP酶通过对肌动蛋白动力学的影响控制许多细胞生物学过程，如细胞迁移、细胞粘附、形态发生和囊泡运输。在神经元中，它们通过调节肌动蛋白细胞骨架参与树突棘形态发生和神经元形态的其他方面。Rho家族成员Cdc 42通过其效应子N-WASP调节树突棘形态，N-WASP激活肌动蛋白成核Arp 2/3复合物。已知兴奋性突触传递调节树突棘中的肌动蛋白动力学，从而引起棘形态或运动性的变化，然而，将谷氨酸受体激活调节至Rho GT3功能的信号通路的细节尚不清楚。PICK 1是PDZ和BAR结构域蛋白，其与Arp 2/3复合物和GTdR Arf 1相互作用以调节树突棘中的肌动蛋白聚合。PICK 1还结合AMPA受体亚单位GluA 2/3，并参与GluA 2依赖性AMPAR运输。在这里，我们表明，PICK 1结合Rac 1和Cdc 42，通过不同的，但重叠的结合位点。此外，AMPAR刺激使Cdc 42失活，并通过PICK 1依赖性过程改变其在神经元中的去污剂溶解度。这项工作表明PICK 1在神经元中将AMPAR刺激转导为Cdc 42功能中的新作用。
PICK1 binds Rac1 and Cdc42. AMPA receptors can interact with Cdc42 via PICK1. AMPA stimulation increases Cdc42 detergent solubility in a PICK1-dependent manner. Rho-family GTPases control numerous cell biological processes via effects on actin dynamics, such as cell migration, cell adhesion, morphogenesis and vesicle traffic. In neurons, they are involved in dendritic spine morphogenesis and other aspects of neuronal morphology via regulation of the actin cytoskeleton. The Rho-family member Cdc42 regulates dendritic spine morphology via its effector N-WASP, which activates the actin-nucleating Arp2/3 complex. Excitatory synaptic transmission is known to regulate actin dynamics in dendritic spines to bring about changes in spine morphology or motility, however, the details of the signalling pathways that transduce glutamate receptor activation to Rho GTPase function are unclear. PICK1 is a PDZ and BAR domain protein that interacts with the Arp2/3 complex and the GTPase Arf1 to regulate actin polymerisation in dendritic spines. PICK1 also binds AMPA receptor subunits GluA2/3 and is involved in GluA2-dependent AMPAR trafficking. Here, we show that PICK1 binds Rac1 and Cdc42, via distinct but overlapping binding sites. Furthermore, AMPAR stimulation deactivates Cdc42 and alters its detergent solubility in neurons via a PICK1-dependent process. This work suggests a novel role for PICK1 in transducing AMPAR stimulation to Cdc42 function in neurons.
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影响因子：
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作者：
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DOI：
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DOI：
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发表时间：
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期刊：
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影响因子：
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