Purkinje Cell Protein 4 Positively Regulates Neurite Outgrowth and Neurotransmitter Release
Purkinje Cell Protein 4 Positively Regulates Neurite Outgrowth and Neurotransmitter Release
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DOI：
10.1002/jnr.22688
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发表时间：
2011-10-01
影响因子：
4.2
通讯作者：
Inagaki, Nobuya
中科院分区：
文献类型：
--
作者：
Harashima, Shin-ichi;Wang, Yu;Inagaki, Nobuya
浦肯野细胞蛋白4（Purkinje cell protein 4，PCP 4），又称脑特异性多肽19（brain-specific polypeptide 19，PEP 19），是一种神经特异性的小分子钙调素结合蛋白，可结合无钙和钙结合钙调素来调节钙调素介导的信号。该分子在阿尔茨海默病、亨廷顿病和酒精中毒的脑中的表达水平降低。然而，很少有人知道PCP 4的功能，神经元或神经内分泌细胞分化和神经递质的释放。为了解决这个问题，我们建立了一个PCP 4四环素诱导的大鼠嗜铬细胞系，PC 12。当PCP 4的表达与多西环素诱导，神经突起生长的神经生长因子（NGF）和二丁酰cAMP，这是抑制W-7，钙调蛋白抑制剂，和PD 98059，ERK抑制剂的存在下，显着先进。此外，在PCP 4诱导的PC 12细胞中，通过用NGF处理，细胞体的大小也增加。在PCP 4诱导的PC 12细胞中，乙酰胆碱和多巴胺的组成性和钾诱发的释放增加，过氧化氢（H2 O2）诱导的凋亡受到抑制。另一方面，敲低PCP 4的siRNA转染减少神经突起的生长和多巴胺的释放，并增加过氧化氢诱导的PC 12细胞凋亡。这些结果表明，PCP 4通过激活钙调蛋白功能促进神经内分泌细胞分化和神经递质释放。(C)2011 Wiley-Liss，Inc.
Purkinje cell protein 4 (PCP4), also called brain-specific polypeptide 19 (PEP19), is a neurospecific, small calmodulin-binding protein that binds both calcium-free and calcium-binding calmodulin to regulate the calmodulin-mediated signal. The expression level of this molecule is decreased in the brain in Alzheimer's disease, Huntington's disease, and alcoholism. However, little is known of the function of PCP4 regarding neuronal or neuroendocrine cell differentiation and neurotransmitter release. To address this, we established a PCP4 tetracycline-inducible rat chromaffin cell line, PC12. When PCP4 expression was induced with doxcycline, neurite outgrowth was significantly advanced in the presence of nerve growth factor (NGF) and dibutyryl cAMP, which was inhibited by W-7, a calmodulin inhibitor, and PD98059, an ERK inhibitor. In addition, size of the cell body also was increased by treatment with NGF in the PCP4-induced PC12 cells. Constitutive and potassium-evoked release of acetylcholine and dopamine was increased and apoptosis induced by hydrogen peroxide (H2O2) was inhibited in PCP4-induced PC12 cells. On the other hand, knockdown of PCP4 by siRNA transfection decreased neurite outgrowth and dopamine release and increased H2O2-induced apoptosis in PC12 cells. These results indicate that PCP4 promotes neuroendocrine cell differentiation and neurotransmitter release by activating calmodulin function. (C) 2011 Wiley-Liss, Inc.