Src mediates endocytosis of TWIK-related acid-sensitive K+ 1 channels in PC12 cells in response to nerve growth factor
Src mediates endocytosis of TWIK-related acid-sensitive K+ 1 channels in PC12 cells in response to nerve growth factor
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Src 介导 PC12 细胞中 TWIK 相关酸敏感 K 1 通道的内吞作用，以响应神经生长因子
DOI：
10.1152/ajpcell.00354.2014
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Matsuoka H and Inoue M
中科院分区：
文献类型：
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作者：
Harada K;Matsuoka H;Fujihara H;Ueta Y;Yanagawa Y;Inoue M;Matsuoka H and Inoue M
Twik相关的酸敏感K+(TASK)通道产生背景K+电流。我们阐明了神经生长因子(NGF)对大鼠肾上腺髓质细胞和PC12细胞的TASK1通道的内化是以依赖于笼蛋白的方式进行的。在这里，我们探索了PC12细胞这种内化的分子机制。酶抑制剂与原肌球蛋白受体激酶A突变体的结合表明，内化是由磷脂酶C和磷脂酰肌醇3-激酶途径介导的，这两个途径会聚到蛋白激酶C上，从而激活非受体酪氨酸激酶Src。NGF诱导的TASK1通道内吞作用在有Src抑制剂的情况下不发生，也不存在激酶死亡的Src突变体的情况下发生。此外，NGF诱导了Src与TASK1通道的瞬时共定位，但不能诱导TASK1突变体，其中370位的酪氨酸被苯丙氨酸取代。该TASK1突变体的酪氨酸磷酸化没有增加，对NGF的内化作用明显减弱。我们认为，NGF通过其羧基末端的酪氨酸磷酸化诱导TASK1通道的内吞。
TWIK-related acid-sensitive K+(TASK) channels produce background K+currents. We elucidated that TASK1 channels in rat adrenal medullary cells and PC12 cells are internalized in a clathrin-dependent manner in response to nerve growth factor (NGF). Here, the molecular mechanism for this internalization in PC12 cells was explored. The combination of enzyme inhibitors with tropomyosin receptor kinase A mutants revealed that the internalization was mediated by both phospholipase C and phosphatidylinositol 3-kinase pathways that converge on protein kinase C with the consequent activation of Src, a nonreceptor tyrosine kinase. The NGF-induced endocytosis of TASK1 channels did not occur in the presence of the Src inhibitor or with the expression of a kinase-dead Src mutant. Additionally, NGF induced a transient colocalization of Src with the TASK1 channel, but not the TASK1 mutant, in which tyrosine at 370 was replaced with phenylalanine. This TASK1 mutant showed no increase in tyrosine phosphorylation and markedly diminished internalization in response to NGF. We concluded that NGF induces endocytosis of TASK1 channels via tyrosine phosphorylation in its carboxyl terminus.