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Abstract：
OBJECTIVE: Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein-protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship.
RESULTS: Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.
RESULTS: Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.
摘要：
目的：视网膜裂和Norrie病分别是由RS1和NDP基因突变引起的X连锁隐性视网膜疾病。两者都可能是单基因的，并且没有报道基因座异质性。然而,有报道显示,在NDP敲除小鼠模型中,Norrie病和视网膜裂孔的特征重叠,并且在视网膜裂孔患者中,这两种基因都参与其中.然而，两种疾病之间的确切分子关系仍未被理解。该研究使用体外和计算机模拟方法调查了视网膜裂素（RS1）和Norrin（NDP）之间的关联。通过共免疫沉淀测定和MALDI-TOF质谱分析了人视网膜中RS1和NDP之间的特异性蛋白质-蛋白质相互作用。STRING数据库用于探索函数关系。
结果：共免疫沉淀表明RS1和NDP之间缺乏直接相互作用，并通过质谱进一步证实。然而,STRING揭示了两种蛋白质之间潜在的间接功能关联。逐步,我们的分析表明,通过PLIN2以及MAP激酶信号通路的FZD4蛋白相互作用组可能是连接视网膜裂孔和Norrie病之间功能关系的纽带.
结果：共免疫沉淀表明RS1和NDP之间缺乏直接相互作用，并通过质谱进一步证实。然而,STRING揭示了两种蛋白质之间潜在的间接功能关联。逐步,我们的分析表明,通过PLIN2以及MAP激酶信号通路的FZD4蛋白相互作用组可能是连接视网膜裂孔和Norrie病之间功能关系的纽带.
