Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells
Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells
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DOI：
10.1093/hmg/9.12.1873
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发表时间：
2000-07-22
影响因子：
3.5
通讯作者：
Trump, D
中科院分区：
文献类型：
--
作者：
Grayson, C;Reid, SNM;Trump, D
X连锁视网膜劈裂症的特征是黄斑区的微囊样改变和视网膜内层内的劈裂，导致男性视力下降。致病基因RS 1的许多错义突变和蛋白质截短突变现已被鉴定，并被认为是失活的。RS 1编码一个224个氨基酸的蛋白质，retinoschisin，它包含一个盘状结构域，但未知的功能。我们已经产生了针对来自视网膜劈裂素内独特区域的肽的多克隆抗体，其检测用二硫苏糖醇还原的视网膜样品中类似于28 kDa的蛋白质，但在非还原条件下大小>40 kDa的多聚体。用该抗体筛选人组织显示视网膜裂素是视网膜特异性的，并且该抗体检测牛和鼠视网膜中类似大小的蛋白质。我们研究了RSIMRNA（用核糖核酸探针原位杂交）和retinoschisin（用免疫组织化学）在视网膜中的表达模式。反义核糖核酸探针只在光感受器层检测到RSIMRNA，但该基因的蛋白产物在光感受器和视网膜内部都存在。此外，分化的视网膜母细胞瘤细胞（Weri-Rb 1细胞）被发现表达RSI mRNA并释放retinoschisin。这些结果表明，retinoschisin由光感受器释放，并在视网膜内层内具有功能。因此，X连锁视网膜劈裂症是由假定的分泌型感光蛋白异常引起的，并且是与视网膜营养不良相关的分泌型感光蛋白的第一个例子。
X-linked retinoschisis is characterized by microcystic-like changes of the macular region and schisis within the inner retinal layers, leading to visual deterioration in males. Many missense and protein-truncating mutations of the causative gene RS1 have now been identified and are thought to be inactivating. RS1 encodes a 224 amino acid protein, retinoschisin, which contains a discoidin domain but is of unknown function. We have generated a polyclonal antibody against a peptide from a unique region within retinoschisin, which detects a protein of similar to 28 kDa in retinal samples reduced with dithiothreitol, but multimers sized >40 kDa under non-reducing conditions. A screen of human tissues with this antibody reveals retinoschisin to be retina specific and the antibody detects a protein of similar size in bovine and murine retinae. We investigated the expression pattern in the retina of both RSI mRNA (using in situ hybridization with riboprobes) and retinoschisin (using immunohistochemistry), The antisense riboprobe detected RSI mRNA only in the photoreceptor layer but the protein product of the gene was present both in the photoreceptors and within the inner portions of the retina. Furthermore, differentiated retinoblastoma cells (Weri-Rb1 cells) were found to express RSI mRNA and to release retinoschisin, These results suggest that retinoschisin is released by photoreceptors and has functions within the inner retinal layers. Thus, X-linked retinoschisis is caused by abnormalities in a putative secreted photoreceptor protein and is the first example of a secreted photoreceptor protein associated with a retinal dystrophy.