FCCA (Forum: Carbohydrates Coming of Age) GLYCODEBUT The Role of O -Glucosylation
FCCA (Forum: Carbohydrates Coming of Age) GLYCODEBUT The Role of O -Glucosylation
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FCCA（论坛：碳水化合物的成熟）GLYCODEBUT O-葡萄糖基化的作用
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通讯作者：
J. Inokuchi
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作者：
M. Jimbo;K. Yamagishi;T. Yamaki;K. Nunomura;K. Kabayama;Y. Igarashi;J. Inokuchi
Notch 信号传导、O-糖基化、O-葡萄糖和温度敏感 摘要 Notch 信号传导在发育过程中调节许多细胞命运决定。在旨在分离该途径新成分的遗传筛选中，新基因 rumi 的突变被确定会导致温度敏感表型。在 28-30 9 C 时，rumi 克隆在所有检查的组织中都表现出成熟的 Notch 表型。然而，在 18±9°C 时，仅出现轻微的 Notch 表型。 Notch 在瘤胃细胞的细胞内和细胞膜中积累，但尽管与 Delta 正常结合，但并未被正确加工。 Rumi 是一种内质网 (ER) 保留蛋白，具有高度保守的 CAP10 结构域。我们的研究表明，Rumi 是一种蛋白 O - 葡萄糖基转移酶 (Poglut)，能够以 O - 连接方式将葡萄糖添加到 Notch 胞外结构域的 EGF 重复序列中共有的 C 1 -X-S-X-P-C 2 序列中的丝氨酸残基上。这些数据表明，Rumi 调节 Notch 折叠和/或追踪，并允许通过内质网中 Notch 的 O-葡萄糖基化在细胞膜上发出信号。在这里，我们与 Hugo Bellen 博士的实验室合作，描述了我们发现鲁米的方法 (1)。我们还强调了功能的重要性
Notch signaling, O-glycosylation, O-glucose, and temperature-sensitive Abstract Notch signaling regulates numerous cell fate deci-sions during development. In a genetic screen designed to isolate new components of this pathway, mutations in a novel gene, rumi , were identiˆed to cause a temperature-sensitive phenotype. At 28–30 9 C, rumi clones exhibited a full-blown Notch phenotype in all the examined tissues. However, at 18 9 C, only a mild Notch phenotype was evident. Notch accumulated intracellularly and in the cell membrane of rumi cells, but was not properly processed despite normal binding to Delta. Rumi is an endoplasmic reticulum (ER)-retained protein with a highly conserved CAP10 domain. Our studies showed that Rumi is a protein O -glucosyltransferase (Poglut), capable of adding glucose in an O -linkage to serine residues in the consensus C 1 -X-S-X-P-C 2 sequence within the EGF repeats of the Notch extracellular domain. These data indicate that Rumi regulates Notch folding and/or tra‹cking and allows signaling at the cell membrane by O -glucosylation of Notch in the ER. Here, we, in collaboration with Dr. Hugo Bellen's laboratory, describe our method of discovery of Rumi (1). We also highlight the functional importance