Acar Melih, Jafar-Nejad Hamed, Takeuchi Hideyuki, Rajan Akhila, Ibrani Dafina, Rana Nadia A, Pan Hongling, Haltiwanger Robert S, Bellen Hugo J
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Cell. 2008 Jan 25;132(2):247-58. doi: 10.1016/j.cell.2007.12.016.
Notch signaling is broadly used to regulate cell-fate decisions. We have identified a gene, rumi, with a temperature-sensitive Notch phenotype. At 28 degrees C-30 degrees C, rumi clones exhibit a full-blown loss of Notch signaling in all tissues tested. However, at 18 degrees C only a mild Notch phenotype is evident. In vivo analyses reveal that the target of Rumi is the extracellular domain of Notch. Notch accumulates intracellularly and at the cell membrane of rumi cells but fails to be properly cleaved, despite normal binding to Delta. Rumi is an endoplasmic reticulum-retained protein with a highly conserved CAP10 domain. Our studies show that Rumi is a protein O-glucosyltransferase, capable of adding glucose to serine residues in Notch EGF repeats with the consensus C1-X-S-X-P-C2 sequence. These data indicate that by O-glucosylating Notch in the ER, Rumi regulates its folding and/or trafficking and allows signaling at the cell membrane.
Notch信号广泛用于调节细胞命运决定。我们鉴定出一个基因rumi，它具有温度敏感的Notch表型。在28摄氏度至30摄氏度时，rumi克隆在所有测试组织中均表现出Notch信号的完全丧失。然而，在18摄氏度时，仅出现轻微的Notch表型。体内分析表明，Rumi的作用靶点是Notch的胞外结构域。Notch在rumi细胞的胞内和细胞膜上积累，但尽管能与Delta正常结合，却无法被正确切割。Rumi是一种保留在内质网中的蛋白质，具有高度保守的CAP10结构域。我们的研究表明，Rumi是一种蛋白质O-葡萄糖基转移酶，能够将葡萄糖添加到Notch EGF重复序列中具有C1-X-S-X-P-C2共有序列的丝氨酸残基上。这些数据表明，通过在内质网中对Notch进行O-糖基化，Rumi调节其折叠和/或运输，并允许在细胞膜上进行信号传导。
