PSD95β regulates plasma membrane Ca(2+) pump localization at the photoreceptor synapse
PSD95β regulates plasma membrane Ca(2+) pump localization at the photoreceptor synapse
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DOI：
10.1016/j.mcn.2009.02.003
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发表时间：
2009-06-01
影响因子：
3.5
通讯作者：
Wijnholds, Jan
中科院分区：
文献类型：
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作者：
Aartsen, Wendy M.;Arsanto, Jean-Pierre;Wijnholds, Jan
在突触前质膜的感光细胞的正确定位的钙挤出机，质膜Ca 2 +-ATP酶（PMCA），是由一个独特的蛋白质复合物。在这里，两个蛋白质的作用内的复杂的膜棕榈酰化蛋白4（MPP 4）和突触后密度蛋白95（PSD 95）进行了研究，更详细地使用Mpp 4和Psd 95突变小鼠。MPP 4缺陷导致PMCA和PSD 95从光感受器突触的损失。MPP 4的C-末端部分的截短导致PSD 95的丢失和PMCA的错误定位，而PSD 95的C-末端部分的截短不影响复合物成员的定位。慢病毒介导的分子置换策略用于在野生型或Mpp 4突变体原代视网膜外植体中选择性表达PSD 95或PSD 95 β。Psd 95基因的沉默导致突触前MPP 4和PMCA 1的丢失。MPP 4和PMCA 1的质膜定位可通过PSD 95 β的表达而恢复。我们的结论是，支架蛋白PSD 95 β和MPP 4是必不可少的调制PMCA水平在突触前质膜，从而影响感光突触钙处理。(C)2009 Elsevier Inc. All rights reserved.
At the presynaptic plasma membrane of the photoreceptor the correct localization of the calcium extruder, plasma membrane Ca2+-ATPase (PMCA), is determined by a unique protein complex. Here, the role of two proteins within the complex; membrane palmitoylated protein 4 (MPP4) and postsynaptic density protein 95 (PSD95) is investigated in more details, using Mpp4 and Psd95 mutant mice. MPP4 deficiency results in the loss of both PMCA and PSD95 from the photoreceptor synapse. Truncation of the C-terminal part of MPP4 leads to a loss of PSD95 and mislocalization of PMCA, while truncation of the C-terminal part of PSD95 did not affect the localization of the complex members. Lentivirus-mediated molecular replacement strategy was used to selectively express either PSD95 or PSD95 beta in wild type or Mpp4 mutant primary retinal explants. Silencing of the Psd95 gene resulted in the loss of presynaptic MPP4 and PMCA1. The plasma membrane localization of MPP4 and PMCA1 could be restored by the expression of PSD95 beta. We conclude that both scaffold proteins PSD95 beta and MPP4 are essential for the modulation of PMCA levels at the presynaptic plasma membrane and thereby influence the photoreceptor synaptic calcium handling. (C) 2009 Elsevier Inc. All rights reserved.