Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.

Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.
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DOI:
10.1083/jcb.200502122
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发表时间:
2005-05-09
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Frohman MA
Frohman MA
中科院分区:
其他
文献类型:
--
作者:
LaLonde MM;Janssens H;Rosenbaum E;Choi SY;Gergen JP;Colley NJ;Stark WS;Frohman MA

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果蝇黑腹果蝇的光传导通过磷脂酶C(PLC)触发的磷脂酰肌醇(PI)脂质修饰的级联反应进行,其中许多步骤仍未确定。我们描述了脂质磷脂酸和产生它的酶,磷脂酶D(PLD)在这一过程中的参与。PLD缺失的果蝇表现出对光的敏感度降低以及对视网膜变性的易感性增加。PLD的过表达使缺乏PLC的果蝇免于光诱导、后紫质介导的退化,并恢复了缺乏PI转移蛋白的果蝇的视觉信号,PI转移蛋白是PLC用于将光刺激转化为神经信号的PI 4,5-二磷酸(PIP2)底物的补充中的关键角色。总之,这些发现表明,PLD通过维持足够的PIP2水平和保护视觉系统免受变紫红质诱导的弱光退化,促进了光转导。
Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)–triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined. We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process. Pld null flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration. Pld overexpression rescues flies lacking PLC from light-induced, metarhodopsin-mediated degeneration and restores visual signaling in flies lacking the PI transfer protein, which is a key player in the replenishment of the PI 4,5-bisphosphate (PIP2) substrate used by PLC to transduce light stimuli into neurological signals. Altogether, these findings suggest that Pld facilitates phototransduction by maintaining adequate levels of PIP2 and by protecting the visual system from metarhodopsin-induced, low light degeneration.
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