The endocytic protein α-adaptin is required for numb-mediated asymmetric cell division in Drosophila

The endocytic protein α-adaptin is required for numb-mediated asymmetric cell division in Drosophila
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DOI:
10.1016/s1534-5807(02)00215-0
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发表时间:
2002-08-01
期刊:
影响因子:
11.8
通讯作者:
Knoblich, JA
Knoblich, JA
中科院分区:
生物学1区
文献类型:
--
作者:
Berdnik, D;Török, T;Knoblich, JA

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在果蝇感觉器官前体细胞的不对称细胞分裂期间,Numb蛋白不对称地定位并分离到一个子细胞中,在那里它通过抑制经由Notch受体的信号转导来影响细胞命运。我们在这里表明,Numb的行为极化分布的α-适应蛋白,参与受体介导的内吞作用。α-适应蛋白结合Numb并以Numb依赖性方式不对称定位。不再与Numb结合的α-适应蛋白的突变形式不能不对称地定位,并在不对称细胞分裂中引起类似于numb的缺陷。我们的研究结果表明,Numb通过极化受体介导的内吞作用下调Notch来影响细胞命运的模型,因为Numb也与Notch的细胞内结构域结合。
During asymmetric cell division in Drosophila sensory organ precursor cells, the Numb protein localizes asymmetrically and segregates into one daughter cell, where it influences cell fate by repressing signal transduction via the Notch receptor. We show here that Numb acts by polarizing the distribution of alpha-Adaptin, a protein involved in receptor-mediated endocytosis. a-Adaptin binds to Numb and localizes asymmetrically in a Numb-dependent fashion. Mutant forms of a-Adaptin that no longer bind to Numb fail to localize asymmetrically and cause numb-like defects in asymmetric cell division. Our results suggest a model in which Numb influences cell fate by downregulating Notch through polarized receptor-mediated endocytosis, since Numb also binds to the intracellular domain of Notch.