Raghu P, Usher K, Jonas S, Chyb S, Polyanovsky A, Hardie R C
Department of Anatomy, Cambridge University, United Kingdom.
Neuron. 2000 Apr;26(1):169-79. doi: 10.1016/s0896-6273(00)81147-2.
Mutations in the Drosophila retinal degeneration A (rdgA) gene, which encodes diacylglycerol kinase (DGK), result in early onset retinal degeneration and blindness. Whole-cell recordings revealed that light-sensitive Ca2+ channels encoded by the trp gene were constitutively active in rdgA photoreceptors. Early degeneration was rescued in rdgA;trp double mutants, lacking TRP channels; however, the less Ca2+-permeable light-sensitive channels (TRPL) were constitutively active instead. No constitutive activity was seen in rdgA;trpI;trp mutants lacking both classes of channel, although, like rdgA;trp, these still showed a residual slow degeneration. Responses to light were restored in rdgA;trp but deactivated abnormally slowly, indicating that DGK is required for response termination. The findings suggest that early degeneration in rdgA is caused by uncontrolled Ca2+ influx and support the proposal that diacylglycerol or its metabolites are messengers of excitation in Drosophila photoreceptors.
果蝇视网膜变性A（rdgA）基因发生突变会导致早发性视网膜变性和失明，该基因编码二酰基甘油激酶（DGK）。全细胞膜片钳记录显示，由trp基因编码的光敏感Ca2+通道在rdgA光感受器中持续激活。在缺乏TRP通道的rdgA;trp双突变体中，早期变性得到挽救；然而，Ca2+通透性较低的光敏感通道（TRPL）反而持续激活。在缺乏这两类通道的rdgA;trpI;trp突变体中未观察到持续激活，尽管与rdgA;trp一样，这些突变体仍表现出残余的缓慢变性。rdgA;trp突变体对光的反应得以恢复，但失活异常缓慢，这表明DGK是反应终止所必需的。这些发现表明，rdgA中的早期变性是由不受控制的Ca2+内流引起的，并支持二酰基甘油或其代谢产物是果蝇光感受器中兴奋信使的观点。
