A direct signaling role for phosphatidylinositol 4,5-bisphosphate (PIP2) in the visual excitation process of microvillar receptors
A direct signaling role for phosphatidylinositol 4,5-bisphosphate (PIP2) in the visual excitation process of microvillar receptors
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DOI：
10.1074/jbc.m414538200
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发表时间：
2005-04-29
影响因子：
4.8
通讯作者：
Nasi, E
中科院分区：
文献类型：
--
作者：
Gomez, MD;Nasi, E
在微绒毛光感受器中，磷脂酶C在光传导中的关键作用是毋庸置疑的，但以前仅用磷脂酰肌醇4，5-二磷酸(PIP2)的下游产物来解释光反应的尝试被证明是不够的。在其他系统中，PIP2已被证明具有自己的信号功能，而不是简单地作为前体分子。由于微绒毛光感受器细胞的光照导致PIP2的破坏，这种磷脂在光传导中的一个潜在作用可能是帮助将转导级联的某些元件(S)保持在非激活状态。我们测试了细胞内透析PIP2对电压钳制的软体动物光感受器的影响，发现光电流的幅度显著降低；相比之下，去极化激活的钙电流和钾电流没有受到影响，从而支持了光信号的特殊作用的概念。在黑暗中，PIP2引起保持电流逐渐外移；这种变化是由于膜电导的下降，可能反映了光敏电导的基开口被抑制。在光敏微绒毛膜斑块中检测了PIP2耗尽的后果，并对光激活离子通道的独有存在进行了筛选。切除后，用抗PIP2抗体灌流可出现单通道电流。外源补充PIP2逆转了这一效应。这些数据支持这样一种观点，即PIP2除了是肌醇三磷酸和二酰甘油的来源外，这两种视觉兴奋信使也可能以直接方式参与光敏电导的控制。
In microvillar photoreceptors the pivotal role of phospholipase C in light transduction is undisputed, but previous attempts to account for the photoresponse solely in terms of downstream products of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis have proved wanting. In other systems PIP2 has been shown to possess signaling functions of its own, rather than simply serving as a precursor molecule. Because illumination of microvillar photoreceptors cells leads to PIP2 breakdown, a potential role for this phospholipid in phototransduction would be to help maintain some element(s) of the transduction cascade in the inactive state. We tested the effect of intracellular dialysis of PIP2 on voltage-clamped molluscan photoreceptors and found a marked reduction in the amplitude of the photocurrent; by contrast, depolarization-activated calcium and potassium currents were unaffected, thus supporting the notion of a specific effect on light signaling. In the dark, PIP2 caused a gradual outward shift of the holding current; this change was due to a decrease in membrane conductance and may reflect the suppression of basal openings of the light-sensitive conductance. The consequences of depleting PIP2 were examined in patches of light-sensitive microvillar membrane screened for the exclusive presence of light-activated ion channels. After excision, superfusion with anti-PIP2 antibodies induced the appearance of single-channel currents. Replenishment of PIP2 by exogenous application reverted the effect. These data support the notion that PIP2, in addition to being the source of inositol trisphosphate and diacylglycerol, two messengers of visual excitation, may also participate in a direct fashion in the control of the light-sensitive conductance.