Proteomic identification of unique photoreceptor disc components reveals the presence of PRCD, a protein linked to retinal degeneration.
Proteomic identification of unique photoreceptor disc components reveals the presence of PRCD, a protein linked to retinal degeneration.
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DOI：
10.1021/pr4003678
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发表时间：
2013-06-07
影响因子：
4.4
通讯作者：
Arshavsky VY
中科院分区：
文献类型：
--
作者：
Skiba NP;Spencer WJ;Salinas RY;Lieu EC;Thompson JW;Arshavsky VY
视觉信号转导发生在称为感光盘的平膜囊泡表面，感光盘位于脊椎动物感光细胞的感光外节细胞器内。虽然生化研究表明椎间盘是由少数高度专业化的蛋白质构成的，但蛋白质组学研究已经产生了包含数百个条目的数据库。我们通过采用蛋白质相关分析来解决这一争议，该分析允许识别可以分级但不能纯化到绝对同质的细胞器的独特成分。我们对圆盘进行连续的分级步骤，并通过无标记定量质谱法确定每个级分中蛋白质的相对量。该分析表明，光感受器盘蛋白质组仅包含十一种成分，满足作为独特的盘驻留成分的标志标准：在分馏步骤中它们之间保持恒定的摩尔比。值得注意的是，其中之一是 PRCD，这种蛋白质的突变已被证明会导致失明，但细胞定位仍然完全未知。将 PRCD 鉴定为一种新型椎间盘特异性蛋白有助于了解其功能作用及其突变的病理生物学意义。我们的研究提供了一个引人注目的例子，蛋白质相关性分析如何区分细胞器的组成成分及其不可避免的污染物。
Visual signal transduction takes place on the surface of flat membrane vesicles called photoreceptor discs, which reside inside the light-sensitive outer segment organelle of vertebrate photoreceptor cells. While biochemical studies have indicated that discs are built with a handful of highly specialized proteins, proteomic studies have yielded databases consisting of hundreds of entries. We addressed this controversy by employing protein correlation profiling which allows identification of unique components of organelles that can be fractionated but not purified to absolute homogeneity. We subjected discs to sequential steps of fractionation and identified the relative amounts of proteins in each fraction by label-free quantitative mass spectrometry. This analysis demonstrated that the photoreceptor disc proteome contains only eleven components, which satisfy the hallmark criterion for being unique disc-resident components: the retention of a constant molar ratio among themselves across fractionation steps. Remarkably, one of them is PRCD, a protein whose mutations have been shown to cause blindness, yet cellular localization remained completely unknown. Identification of PRCD as a novel disc-specific protein facilitates understanding its functional role and the pathobiological significance of its mutations. Our study provides a striking example how protein correlation profiling allows a distinction between constitutive components of cellular organelles and their inevitable contaminants.
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影响因子：
4.4
作者：
Han, Zhou;Anderson, David W.;Papermaster, David S.
通讯作者：
Papermaster, David S.
影响因子：
4
作者：
Nevet, M. J.;Shalev, S. A.;Ben-Yosef, T.
通讯作者：
Ben-Yosef, T.
影响因子：
64.5
作者：
Foster, LJ;de Hoog, CL;Mann, M
通讯作者：
Mann, M
DOI：
10.1085/jgp.58.3.225
发表时间：
1971-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Bownds D;Gordon-Walker A;Gaide-Huguenin AC;Robinson W
通讯作者：
Robinson W
DOI：
10.1523/jneurosci.0613-10.2010
发表时间：
2010-05-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lobanova ES;Herrmann R;Finkelstein S;Reidel B;Skiba NP;Deng WT;Jo R;Weiss ER;Hauswirth WW;Arshavsky VY
通讯作者：
Arshavsky VY