Drosophila nicastrin is essential for the intramembranous cleavage of Notch
Drosophila nicastrin is essential for the intramembranous cleavage of Notch
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DOI：
10.1016/s1534-5807(01)00109-5
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发表时间：
2002-01-01
影响因子：
11.8
通讯作者：
St Johnston, D
中科院分区：
文献类型：
--
作者：
López-Schier, H;St Johnston, D
γ-分泌酶的催化亚基被认为是早老素，其是APP裂解和Notch加工所需的。早老素存在于多亚基复合物中，该复合物还含有Nicastrin。Nicastrin与APP加工有关，但其在Notch信号传导中的作用仍不清楚。在这里，我们表明，果蝇Nicastrin是所需的Notch信号，并特别在S3裂解步骤的行为。部分加工的Notch在nicastrin和早老素突变体卵泡细胞的顶部积累。nicastrin和早老素突变也破坏血影蛋白细胞骨架，表明γ-分泌酶复合物在果蝇中除了在加工Notch和APP中的作用外还有另一种功能。
The catalytic subunit of gamma-secretase is thought to be Presenilin, which is required for both the cleavage of APP and in the processing of Notch. Presenilin is found in a multisubunit complex that also contains Nicastrin. Nicastrin has been implicated in APP processing, but its role in Notch signaling remains unclear. Here we show that Drosophila Nicastrin is required for Notch signaling, and acts specifically at the S3 cleavage step. Partially processed Notch accumulates apically in nicastrin and presenilin mutant follicle cells. nicastrin and presenilin mutations also disrupt the spectrin cytoskeleton, suggesting that the gamma-secretase complex has another function in Drosophila in addition to its role in processing Notch and APP.