Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation
Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation
复制标题
DOI：
10.1016/j.neuron.2004.09.020
复制
发表时间：
2004-10-14
期刊：
影响因子：
16.2
通讯作者：
Gillespie, PG
中科院分区：
文献类型：
--
作者：
Hirono, M;Denis, CS;Gillespie, PG
在响应于机械刺激而打开后，毛细胞转导通道以各自依赖于Call的快速和缓慢机制进行适应。我们在这里证明，转导和适应需要磷脂酰肌醇4，5-二磷酸（PIP 2）的正常动力学。PlP（2）在毛细胞中的分布非常显著，但不分布于毛束的基底部和蛙囊状毛细胞的顶面。磷脂酰肌醇脂质磷酸酶Ptprq定位于这些无PIP 2的结构域，表明Ptprq在那里维持低PIP 2水平。通过抑制磷脂酰肌醇4-激酶或通过氨基糖苷类螯合来消耗PIP 2降低了快速和缓慢适应的速率。PIP 2和其他阴离子磷脂直接与肌球蛋白-1c的10个结构域结合，肌球蛋白-1c是介导缓慢适应的马达，允许与膜的强烈相互作用，并可能调节马达的活性。P1 P2耗尽还引起转导电流的损失。因此，P1 P2在毛细胞适应和转导中起重要作用。
After opening in response to mechanical stimuli, hair cell transduction channels adapt with fast and slow mechanisms that each depend on Call. We demonstrate here that transduction and adaptation require phosphatidylinositol 4,5-bisphosphate (PIP2) for normal kinetics. PlP(2) has a striking distribution in hair cells, being excluded from the basal region of hair bundles and apical surfaces of frog saccular hair cells. Localization of a phosphatidylinositol lipid phosphatase, Ptprq, to these PlP(2)-free domains suggests that Ptprq maintains low PIP2 levels there. Depletion of PIP2 by inhibition of phosphatidylinositol 4-kinase or sequestration by aminoglycosides reduces the rates of fast and slow adaptation. PIP2 and other anionic phospholipids bind directly to the 10 domains of myosin-1c, the motor that mediates slow adaptation, permitting a strong interaction with membranes and likely regulating the motor's activity. PlP2 depletion also causes a loss in transduction current. PlP2 therefore plays an essential role in hair cell adaptation and transduction.