Sphingosine kinases and their metabolites modulate endolysosomal trafficking in photoreceptors.
Sphingosine kinases and their metabolites modulate endolysosomal trafficking in photoreceptors.
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DOI：
10.1083/jcb.201004098
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发表时间：
2011-02-21
期刊：
影响因子：
--
通讯作者：
Acharya U
中科院分区：
文献类型：
--
作者：
Yonamine I;Bamba T;Nirala NK;Jesmin N;Kosakowska-Cholody T;Nagashima K;Fukusaki E;Acharya JK;Acharya U
鞘氨醇激酶活性的改变改变了溶酶体对视紫红质和瞬时受体电位(Trp)通道的降解率，并可导致视网膜变性。内化的膜蛋白要么被转运到晚期的内小体和溶酶体进行降解，要么被循环到质膜。尽管参与运输和分选的蛋白质已经得到了很好的研究，但对调节膜蛋白在细胞内运输的脂分子知之甚少。我们以果蝇黑腹果蝇光感受器为模型系统，研究了鞘氨醇及其代谢产物在内体转运中的作用。功能获得和功能丧失分析表明，鞘氨醇激酶通过调节二氢鞘氨醇1磷酸(DHS1P)和鞘氨醇1磷酸(S1P)水平，影响G蛋白偶联受体视紫红质和光敏瞬时受体电位(TRP)通道的运输。相对于S1P，DHS1P水平的增加导致视紫红质和色氨酸的溶酶体降解增强，并导致野生型感光细胞的视网膜退化。我们的结果表明，鞘氨醇及其代谢物通过影响视紫红质和色氨酸的内体转运来调节光感受器的动态平衡。
Alterations in sphingosine kinase activity change the degradation rates of Rhodopsin and the transient receptor potential (TRP) channel by lysosomes and can result in retinal degeneration. Internalized membrane proteins are either transported to late endosomes and lysosomes for degradation or recycled to the plasma membrane. Although proteins involved in trafficking and sorting have been well studied, far less is known about the lipid molecules that regulate the intracellular trafficking of membrane proteins. We studied the function of sphingosine kinases and their metabolites in endosomal trafficking using Drosophila melanogaster photoreceptors as a model system. Gain- and loss-of-function analyses show that sphingosine kinases affect trafficking of the G protein–coupled receptor Rhodopsin and the light-sensitive transient receptor potential (TRP) channel by modulating the levels of dihydrosphingosine 1 phosphate (DHS1P) and sphingosine 1 phosphate (S1P). An increase in DHS1P levels relative to S1P leads to the enhanced lysosomal degradation of Rhodopsin and TRP and retinal degeneration in wild-type photoreceptors. Our results suggest that sphingosine kinases and their metabolites modulate photoreceptor homeostasis by influencing endolysosomal trafficking of Rhodopsin and TRP.
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