Chakrabarti Purbani, Kolay Sourav, Yadav Shweta, Kumari Kamalesh, Nair Amit, Trivedi Deepti, Raghu Padinjat
Inositide Laboratory, Babraham Institute, Cambridge, United Kingdom.
National Centre for Biological Sciences, TIFR-GKVK Campus, Bangalore, India; Manipal University, Madhav Nagar, Manipal, Karnataka, India.
PLoS Genet. 2015 Jan 29;11(1):e1004948. doi: 10.1371/journal.pgen.1004948. eCollection 2015 Jan.
Multiple PIP2 dependent molecular processes including receptor activated phospholipase C activity occur at the neuronal plasma membranes, yet levels of this lipid at the plasma membrane are remarkably stable. Although the existence of unique pools of PIP2 supporting these events has been proposed, the mechanism by which they are generated is unclear. In Drosophila photoreceptors, the hydrolysis of PIP2 by G-protein coupled phospholipase C activity is essential for sensory transduction of photons. We identify dPIP5K as an enzyme essential for PIP2 re-synthesis in photoreceptors. Loss of dPIP5K causes profound defects in the electrical response to light and light-induced PIP2 dynamics at the photoreceptor membrane. Overexpression of dPIP5K was able to accelerate the rate of PIP2 synthesis following light induced PIP2 depletion. Other PIP2 dependent processes such as endocytosis and cytoskeletal function were unaffected in photoreceptors lacking dPIP5K function. These results provide evidence for the existence of a unique dPIP5K dependent pool of PIP2 required for normal Drosophila phototransduction. Our results define the existence of multiple pools of PIP2 in photoreceptors generated by distinct lipid kinases and supporting specific molecular processes at neuronal membranes.
包括受体激活的磷脂酶C活性在内的多种依赖磷脂酰肌醇-4,5-二磷酸（PIP2）的分子过程发生在神经元质膜上，然而质膜上这种脂质的水平却非常稳定。尽管有人提出存在支持这些事件的独特PIP2池，但它们的产生机制尚不清楚。在果蝇光感受器中，G蛋白偶联的磷脂酶C活性对PIP2的水解对于光子的感觉转导至关重要。我们确定果蝇磷脂酰肌醇-4-磷酸-5-激酶（dPIP5K）是光感受器中PIP2重新合成所必需的一种酶。dPIP5K的缺失会导致光感受器膜对光的电反应以及光诱导的PIP2动态变化出现严重缺陷。dPIP5K的过表达能够在光诱导的PIP2耗尽后加速PIP2的合成速率。其他依赖PIP2的过程，如内吞作用和细胞骨架功能，在缺乏dPIP5K功能的光感受器中不受影响。这些结果为正常果蝇光转导所需的独特的依赖dPIP5K的PIP2池的存在提供了证据。我们的结果确定了光感受器中由不同脂质激酶产生并支持神经元膜上特定分子过程的多个PIP2池的存在。
