Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs
Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs
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PICK1 的破坏会削弱 ASIC 的功能以及 ASIC 的 PKC 监管
DOI：
10.1152/ajpcell.00569.2009
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发表时间：
2010-12-01
影响因子：
5.5
通讯作者：
Wang, Fang
中科院分区：
文献类型：
--
作者：
Hu, Zhuang-Li;Huang, Chao;Wang, Fang
胡志良，黄春，付华，金英，吴文宁，熊庆杰，谢南，龙玲玲，陈建国，王芳。PICK 1的破坏减弱ASICs的功能和PKC对ASICs的调节。美国生理学杂志细胞生理学299：C1355-C1362，2010年。首次发表于2010年9月8日; doi：10.1152/ajpcell.00569.2009。酸敏感离子通道（Acid-sensing ion channels，ASICs）广泛存在于中枢和外周神经系统，参与多种生理和病理过程。与C激酶1（PICK 1）相互作用的蛋白被克隆为与蛋白激酶C（PKC）相互作用的蛋白之一，并与ASIC 1和ASIC 2共定位。本研究以PICK 1基因敲除（PICK 1-KO）C57/BL 6小鼠为研究对象，结合全细胞膜片钳、钙离子成像、RT-PCR、Western blot和免疫细胞化学等技术，探讨了ASICs的可能变化以及PKC对ASICs的调控作用。结果表明，PICK 1在ASIC功能调节中起关键作用。在PICK 1-KO小鼠皮层神经元中，酸介导的ASIC电流幅度和[Ca 2 +]（i）升高均降低，这归因于质膜ASIC 1a和ASIC 2a蛋白表达的降低。PKC是PICK 1的伴侣蛋白，通过PICK 1调节ASIC的功能。PKC的激动剂和拮抗剂仅改变野生型小鼠的ASIC电流和酸诱导的[Ca 2 +]（i）增加，但在KO小鼠中不改变。总之，我们的数据提供了来自PICK 1-KO小鼠的直接证据，即一种新的靶蛋白PICK 1将调节大脑中ASIC功能和膜表达。此外，PICK 1在PKC和ASICs之间起着桥梁作用。
Hu ZL, Huang C, Fu H, Jin Y, Wu WN, Xiong QJ, Xie N, Long LH, Chen JG, Wang F. Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs. Am J Physiol Cell Physiol 299: C1355-C1362, 2010. First published September 8, 2010; doi:10.1152/ajpcell.00569.2009.-Acid-sensing ion channels (ASICs) extensively exist in both central and peripheral neuronal systems and contribute to many physiological and pathological processes. The protein that interacts with C kinase 1 (PICK1) was cloned as one of the proteins interacting with protein kinase C (PKC) and colocalized with ASIC1 and ASIC2. Here, we used PICK1 knockout (PICK1-KO) C57/BL6 mice together with the whole cell patch clamp, calcium imaging, RT-PCR, Western blot, and immunocytochemistry techniques to explore the possible change in ASICs and the regulatory effects of PKC on ASICs. The results showed that PICK1 played a key role in regulation of ASIC functions. In PICK1-KO mouse cortical neurons, both the amplitude of ASIC currents and elevation of [Ca2+](i) mediated by acid were decreased, which were attributable to the decreased expression of ASIC1a and ASIC2a proteins in the plasma membrane. PKC, a partner protein of PICK1, regulated ASIC functions via PICK1. The agonist and antagonist of PKC only altered ASIC currents and acid-induced increase in [Ca2+](i) in wild-type, but not in KO mice. In conclusion, our data provided the direct evidence from PICK1-KO mice that a novel target protein, PICK1, would regulate ASIC function and membrane expression in the brain. In addition, PICK1 played the bridge role between PKC and ASICs.