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首页> 外文期刊>Experimental Eye Research >The progressive rod-cone degeneration (PRCD) protein is secreted through the conventional ER/Golgi-dependent pathway
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The progressive rod-cone degeneration (PRCD) protein is secreted through the conventional ER/Golgi-dependent pathway

机译：渐进性杆锥变性（PRCD）蛋白是通过常规ER /高尔基体依赖性途径分泌的

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摘要

Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration. Mutations of the PRCD gene are associated with RP in both dogs and humans. To date, four distinct PRCD mutations have been reported worldwide. Here we report the clinical phenotype of another patient with PRCD mutations, carrying the known p.R18X mutation and a novel missense mutation, p.P25T. This mutation affects a highly conserved amino acid, is predicted to be damaging by several prediction tools, and was not found in the public databases or in 115 ethnically-matched control individuals. The phenotype of this patient resembles that of previously reported patients with PRCD mutations, including bull's eye mac-ulopathy, which appears to be a hallmark of the PRCD-induced phenotype. PRCD encodes for a 54 amino acids long protein with unknown function. The first 20 amino acids appear to encode for a signal peptide (SP), suggesting that PRCD is a secreted protein. To study PRCD secretion, C-terminally myc-tagged PRCD was expressed in cultured cells. Cells and conditioned media were analyzed by Western blot. PRCD was found in both cell extracts and media. However, a truncated PRCD protein lacking the first 20 amino acids was present only in cell extracts and not in media, confirming that PRCD extracellular secretion is mediated by its N-terminal SP. To characterize the secretory pathway of PRCD, various pharmacological agents which interfere with transport of proteins through the ER and Golgi to the plasma membrane were used. PRCD secretion was significantly inhibited by all tested pharmacological agents, confirming that it is secreted through the classic ER/Golgi-dependent secretory pathway. We tested the effect of two mutations on the PRCD protein, and found that p.C2Y, but not p.P25T, affects protein stability, and that neither mutation affects secretion. Our data suggest that PRCD functions as a secreted protein. These findings shed a new light on PRCD function and the etiology of RP.
机译：色素性视网膜炎（RP）是遗传性视网膜变性的最常见形式。在狗和人中，PRCD基因的突变均与RP相关。迄今为止，全世界已经报道了四种不同的PRCD突变。在这里，我们报告了另一名带有PRCD突变的患者的临床表型，携带已知的p.R18X突变和新型错义突变p.P25T。这种突变会影响高度保守的氨基酸，预计会被几种预测工具破坏，并且在公共数据库或115个种族匹配的对照个体中均未发现。该患者的表型类似于先前报道的具有PRCD突变的患者，包括牛眼黄斑病变，这似乎是PRCD诱导的表型的标志。 PRCD编码功能未知的54个氨基酸长的蛋白质。前20个氨基酸似乎编码信号肽（SP），表明PRCD是一种分泌蛋白。为了研究PRCD的分泌，在培养细胞中表达了C末端带有myc标签的PRCD。通过蛋白质印迹分析细胞和条件培养基。在细胞提取物和培养基中均发现了PRCD。但是，缺少前20个氨基酸的截短的PRCD蛋白仅存在于细胞提取物中，而不存在于培养基中，这证明PRCD的细胞外分泌是由其N末端SP介导的。为了表征PRCD的分泌途径，使用了各种干扰蛋白质通过ER和高尔基体向质膜运输的药理剂。所有经过测试的药理剂均显着抑制PRCD的分泌，从而证实它是通过经典的ER /高尔基依赖性分泌途径分泌的。我们测试了两个突变对PRCD蛋白的影响，发现p.C2Y而不是p.P25T影响蛋白质稳定性，并且两个突变均不影响分泌。我们的数据表明PRCD起着分泌蛋白的作用。这些发现为PRCD的功能和RP的病因学提供了新的思路。

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