An outer segment localization signal at the C terminus of the photoreceptor-specific retinol dehydrogenase
An outer segment localization signal at the C terminus of the photoreceptor-specific retinol dehydrogenase
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DOI：
10.1523/jneurosci.5302-03.2004
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发表时间：
2004-03-17
影响因子：
5.3
通讯作者：
Nathans, J
中科院分区：
文献类型：
--
作者：
Luo, WQ;Marsh-Armstrong, N;Nathans, J
光感受器视黄醇脱氢酶（prRDH）是定位于视杆和视锥的外节（OS）的膜相关胞质蛋白。在这里，我们证明了C-末端16个氨基酸的prRDH赋予膜协会以及锥和杆OS针对连接的绿色荧光蛋白。在转染的293细胞和转基因非洲爪蟾光感受器的膜协会介导的脂肪酰化在一个或多个进化上保守的半胱氨酸内的prRDH C-末端尾部。在牛OS中，天然prRDH类似地被酰化，并且该键的水解从膜释放蛋白质。有效的OS定位需要膜结合和prRDH序列。（V/I）XPX在极端的C末端，这非常类似的C-末端序列的目标视蛋白/视紫红质的OS。综合考虑，这些数据表明，C-末端的...（V/I）XPX序列是一种通用的OS定位信号，可以在整合和外周膜蛋白的背景下发挥作用。OS定位的这种策略类似于用于蛋白质定位到线粒体、过氧化物酶体、核内体和内质网的那些策略;在每种情况下，靶向相同亚细胞目的地的结构不同的蛋白质之间共享短的N-或C-末端序列。
Photoreceptor retinol dehydrogenase (prRDH) is a membrane- associated cytosolic protein that localizes to the outer segments ( OS) of rods and cones. Here, we demonstrate that the C-terminal 16 amino acids of prRDH confer membrane association as well as cone and rod OS targeting on a linked green fluorescent protein. Membrane association in transfected 293 cells and in transgenic Xenopus photoreceptors is mediated by fatty acylation at one or more evolutionarily conserved cysteines within the prRDH C-terminal tail. In bovine OS, native prRDH is similarly acylated, and hydrolysis of this linkage releases the protein from the membrane. Efficient OS localization requires both membrane association and the prRDH sequence... (V/I) XPX at the extreme C terminus, which closely resembles the C-terminal sequence that targets opsin/rhodopsin to the OS. Taken together, these data imply that the C-terminal... (V/I) XPX sequence is a general OS localization signal that can function in the context of both integral and peripheral membrane proteins. This strategy for OS localization resembles those used for protein localization to mitochondria, peroxisomes, endosomes, and endoplasmic reticulum; in each case, a short N- or C-terminal sequence is shared among structurally diverse proteins that are targeted to the same subcellular destination.