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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Differential roles for NSF and GRIP/ABP in AMPA receptor cycling
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Differential roles for NSF and GRIP/ABP in AMPA receptor cycling

机译:NSF和GRIP / ABP在AMPA受体循环中的差异作用

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摘要

α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) stability and movement at synapses are important factors controlling synaptic strength. Here, we study the roles of proteins [N-ethylmaleimide-sensitive fusion protein (NSF), glutamate receptor AMPAR binding protein (ABP)-interacting protein (GRIP)/(ABP), and protein interacting with C-kinase-1 (PICK1) that interact with the GluR2 subunit in the control of the surface expression and cycling of AMPARs. Epitope-tagged GluR2 formed functional receptors that exhibited targeting to synaptic sites. Constructs in which binding to NSF, PDZ proteins (GRIP/ABP and PICK1), or GRIP/ABP alone was eliminated each exhibited normal surface targeting and constitutive cycling. The lack of NSF binding, however, resulted in receptors that were endocytosed to a greater extent than wild-type receptors in response to application of AMPA or N-methyl-D-aspartate (NMDA). Conversely, the behavior of the GluR2 mutants incapable of binding to GRIP/ABP suggests that these PDZ proteins play a role in the stabilization of an intracellular pool of AMPARs that have been internalized on stimulation, thus inhibiting their recycling to the synaptic membrane. These results provide further evidence for distinct functional roles of GluR2-interacting proteins in AMPAR trafficking.
机译:α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体(AMPAR)的稳定性和突触运动是控制突触强度的重要因素。在这里,我们研究蛋白质[N-乙基马来酰亚胺敏感融合蛋白(NSF),谷氨酸受体AMPAR结合蛋白(ABP)相互作用蛋白(GRIP)/(ABP)以及与C激酶-1(PICK1相互作用)的蛋白质的作用)与GluR2亚基相互作用,控制AMPAR的表面表达和循环。带有表位标记的GluR2形成功能性受体,该受体表现出对突触位点的靶向作用。消除了与NSF,PDZ蛋白(GRIP / ABP和PICK1)或单独的GRIP / ABP结合的构建体均表现出正常的表面靶向性和本构循环。但是,由于缺乏NSF结合,响应于AMPA或N-甲基-D-天门冬氨酸(NMDA)的应用,导致受体的内吞作用比野生型受体更大。相反,不能与GRIP / ABP结合的GluR2突变体的行为表明,这些PDZ蛋白在稳定AMPARs的细胞内池中发挥了作用,该池在刺激后被内在化,从而抑制了它们在突触膜上的再循环。这些结果为GluR2相互作用蛋白在AMPAR运输中的独特功能作用提供了进一步的证据。

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