Cologne Center for Genomics, Universität zu Köln, 50931 Köln, Germany.
J Biol Chem. 2011 Oct 28;286(43):37665-75. doi: 10.1074/jbc.M111.267971. Epub 2011 Aug 24.
Loss-of-function mutations in the gene COH1, also known as VPS13B, lead to autosomal recessive Cohen syndrome. However, the cellular distribution and function of the encoded protein COH1 (3997 amino acids), which lacks functional homologies to other mammalian proteins, have remained enigmatic. We show here that COH1 is a peripheral Golgi membrane protein that strongly co-localizes with the cis-Golgi matrix protein GM130. Consistent with its subcellular localization, COH1 depletion using RNAi causes fragmentation of the Golgi ribbon into ministacks. Disruption of Golgi organization observed in fibroblasts from Cohen syndrome patients suggests that Golgi dysfunction contributes to Cohen syndrome pathology. In conclusion, our findings establish COH1 as a Golgi-associated matrix protein required for Golgi integrity.
COH1 基因（也称为 VPS13B）的功能丧失突变导致常染色体隐性遗传的 Cohen 综合征。然而，编码蛋白 COH1（3997 个氨基酸）缺乏与其他哺乳动物蛋白的功能同源性，其细胞分布和功能仍然是个谜。我们在这里表明，COH1 是一种外周高尔基体膜蛋白，与顺式高尔基体基质蛋白 GM130 强烈共定位。与它的亚细胞定位一致，使用 RNAi 耗尽 COH1 会导致高尔基体带裂成小片段。在 Cohen 综合征患者的成纤维细胞中观察到的高尔基体组织的破坏表明，高尔基体功能障碍导致 Cohen 综合征的病理学。总之，我们的发现将 COH1 确定为高尔基体相关基质蛋白，是高尔基体完整性所必需的。
