Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic accumulation of F-actin
Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic accumulation of F-actin
复制标题
DOI：
10.1074/jbc.m210802200
复制
发表时间：
2003-03-21
影响因子：
4.8
通讯作者：
Sobue, K
中科院分区：
文献类型：
--
作者：
Usui, S;Konno, D;Sobue, K
PSD-Zip 45/Homer 1c包含使能/VASP同源1（EVH 1）结构域和亮氨酸拉链基序，是与代谢型谷氨酸受体和胫家族相互作用的突触后密度（PSD）支架蛋白。我们研究了PSD-Zip 45在培养的海马神经元中突触靶向的分子机制。EVH 1结构域和末端C-末端亮氨酸拉链基序是其突触靶向的分子决定因素。EVH 1结构域的突变体或极端C-末端亮氨酸拉链基序的缺失的过度表达显着抑制内源性小腿的突触定位，但不是PSD-95或GKAP。与此相反，过表达的GKAP突变体缺乏柄结合活性的柄的突触定位没有影响。肌动蛋白解聚latrunculin A减少突触定位的PSD-Zip 45，小腿，和F-肌动蛋白，但不是PSD-95或GKAP。PSD-Zip 45的过表达增强了突触F-肌动蛋白的积累。此外，过度表达。PSD-Zip 45和柄的同种型诱导的突触扩大与突触F-肌动蛋白的进一步积累有关。PSD-Zip 45的EVH 1结构域和极端C-末端亮氨酸拉链基序对于这些事件也是至关重要的。因此，这些数据表明PSD-Zip 45-柄和PSD-95-GKAP复合物形成不同的突触隔室，并且单独的PSD-Zip 45或PSD-Zip 45-柄参与F-肌动蛋白的突触积累。
PSD-Zip45/Homer1c, which contains an enabled/VASP homology 1 (EVH1) domain and leucine zipper motifs, is a postsynaptic density (PSD) scaffold protein that interacts with metabotropic glutamate receptors and the shank family. We studied the molecular mechanism underlying the synaptic targeting of PSD-Zip45 in cultured hippocampal neurons. The EVH1 domain and the extreme C-terminal leucine zipper motif were molecular determinants for its synaptic targeting. The overexpression of the mutant of the EVH1 domain or deletion of the extreme C-terminal leucine zipper motif markedly suppressed the synaptic localization of endogenous shank but not PSD-95 or GKAP. In contrast, an overexpressed GKAP mutant lacking shank binding activity had no effect on the synaptic localization of shank. Actin depolymerization by latrunculin A reduced the synaptic localization of PSD-Zip45, shank, and F-actin but not of PSD-95 or GKAP. Overexpression of PSD-Zip45 enhanced the accumulation of synaptic F-actin. Additionally, overexpression. of PSD-Zip45 and an isoform of shank induced synaptic enlargement in association with the further accumulation of synaptic F-actin. The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45 were also critical for these events. Thus, these data suggest that the PSD-Zip45-shank and PSD-95-GKAP complexes form different synaptic compartments, and PSD-Zip45 alone or PSD-Zip45-shank is involved in the synaptic accumulation of F-actin.