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首页> 外文期刊>Neuron >Clathrin Adaptor AP2 and NSF Interact with Overlapping Sites of GluR2 and Play Distinct Roles in AMPA Receptor Trafficking and Hippocampal LTD.
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Clathrin Adaptor AP2 and NSF Interact with Overlapping Sites of GluR2 and Play Distinct Roles in AMPA Receptor Trafficking and Hippocampal LTD.

机译:网格蛋白适配器AP2和NSF与GluR2的重叠位点相互作用,并在AMPA受体贩运和海马有限公司中发挥不同的作用。

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摘要

Proteins that bind to the cytoplasmic tails of AMPA receptors control receptor trafficking and thus the strength of postsynaptic responses. Here we show that AP2, a clathrin adaptor complex important for endocytosis, associates with a region of GluR2 that overlaps the NSF binding site. Peptides used previously to interfere with NSF binding also antagonize GluR2-AP2 interaction. Using GluR2 mutants and peptide variants that dissociate NSF and AP2 interaction, we find that AP2 is involved specifically in NMDA receptor-induced (but not ligand-dependent) internalization of AMPA receptors, and is essential for hippocampal long-term depression (LTD). NSF function, on the other hand, is needed to maintain synaptic AMPA receptor responses, but is not directly required for NMDA receptor-mediated internalization and LTD.
机译:结合到AMPA受体胞质尾部的蛋白质控制着受体的运输,从而控制了突触后反应的强度。在这里,我们显示AP2,一种对内吞作用重要的网格蛋白衔接子复合物,与GluR2的一个区域重叠,该区域与NSF结合位点重叠。以前用来干扰NSF结合的肽也拮抗GluR2-AP2相互作用。使用分离NSF和AP2相互作用的GluR2突变体和肽变体,我们发现AP2特别参与NMDA受体诱导的AMPA受体内化(但不依赖配体),对于海马长期抑郁症(LTD)至关重要。另一方面,NSF功能是维持突触AMPA受体反应所必需的,但NMDA受体介导的内在化和LTD并非直接需要。

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