Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression
Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression
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DOI：
10.1073/pnas.211132798
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Huganir, RL
中科院分区：
文献类型：
--
作者：
Kim, CH;Chung, HJ;Huganir, RL
含有PDZ结构域的蛋白与α-氨基-3-羟基-5-甲基异恶唑丙酸(AMPA)受体C末端的相互作用在受体靶向兴奋性突触的调节中起重要作用。最近的研究表明，突触上AMPA受体的快速内化可能至少部分地介导了长期抑郁(LTD)的表达。我们以前已经证明，AMPA受体GluR2亚基上的Ser-880的磷酸化差异地调节了GluR2与含有PDZ结构域的蛋白GRIN和PICK1的相互作用。在这里，我们发现在海马片诱导LTD增加了GluR2 C末端PDZ配体中Ser-880的磷酸化，提示GluR2与GRIP1和PICK1相互作用的调节可能调节LTD过程中AMPA受体的内化。此外，突触后细胞内灌流GluR2 C端肽可以破坏GluR2与PICK1的相互作用，从而抑制海马LTD的表达。这些结果表明，GluR2与PICK1的相互作用可能对LTD在海马区的表达起到调节作用。
The interaction of PDZ domain-containing proteins with the C termini of alpha -amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors has been suggested to be important in the regulation of receptor targeting to excitatory synapses. Recent studies have shown that the rapid internalization of AMPA receptors at synapses may mediate, at least in part, the expression of long-term depression (LTD). We have previously shown that phosphorylation of Ser-880 on the AMPA receptor GluR2 subunit differentially regulated the interaction of GluR2 with the PDZ domain-containing proteins GRIN and PICK1. Here, we show that induction of LTD in hippocampal slices increases phosphorylation of Ser-880 within the GluR2 C-terminal PDZ ligand, suggesting that the modulation of GluR2 interaction with GRIP1 and PICK1 may regulate AMPA receptor internalization during LTD. Moreover, postsynaptic intracellular perfusion of GluR2 C-terminal peptides that disrupt GluR2 interaction with PICK1 inhibit the expression of hippocampal LTD. These results suggest that the interaction of GluR2 with PICK1 may play a regulatory role in the expression of LTD in the hippocampus.