Regulation of membrane localization of sanpodo by lethal giant larvae and neuralized in asymmetrically dividing cells of Drosophila sensory organs
Regulation of membrane localization of sanpodo by lethal giant larvae and neuralized in asymmetrically dividing cells of Drosophila sensory organs
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DOI：
10.1091/mbc.e05-03-0177
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发表时间：
2005-08-01
影响因子：
3.3
通讯作者：
Jan, YN
中科院分区：
文献类型：
--
作者：
Roegiers, F;Jan, LY;Jan, YN
在果蝇中，不对称分裂发生在中枢和外周神经系统（PNS）的神经前体细胞增殖期间，其中膜相关蛋白Numb在细胞分裂期间不对称定位，并在有丝分裂后分离到两个子细胞之一（pIIb细胞）。Numb在遗传学上被证明是Notch信号传导的拮抗剂，也是Sanpodo膜定位的负调节剂，Sanpodo是CNS中不对称细胞分裂期间Notch信号传导所需的四次跨膜蛋白。以前，我们确定了致命的巨大幼虫（lgl）作为所需的基因在成年PNS中的Notch介导的抑制。在这项研究中，我们表明，Sanpodo的表达在不对称分裂的前体细胞的PNS和Sanpodo的内化在pIIb细胞是依赖于细胞内相关的LGL。Lgl特异性地调节Sanpodo的内化，可能通过内吞作用，但不是内吞作用Delta所需的，内吞作用Delta是不对称细胞分裂期间Notch介导的细胞命运决定中所需的步骤。相反，神经化的E3泛素连接酶是Delta内吞作用和Sanpodo内化所必需的。这项研究确定了迄今未报道的作用，Lgl作为Sanpodo在成人PNS的不对称细胞分裂过程中的调节剂。
In Drosophila, asymmetric division occurs during proliferation of neural precursors of the central and peripheral nervous system (PNS), where a membrane-associated protein, Numb, is asymmetrically localized during cell division and is segregated to one of the two daughter cells (the pIIb cell) after mitosis. numb has been shown genetically to function as an antagonist of Notch signaling and also as a negative regulator of the membrane localization of Sanpodo, a four-pass transmembrane protein required for Notch signaling during asymmetric cell division in the CNS. Previously, we identified lethal giant larvae (lgl) as a gene required for numb-mediated inhibition of Notch in the adult PNS. In this study we show that Sanpodo is expressed in asymmetrically dividing precursor cells of the PNS and that Sanpodo internalization in the pIIb cell is dependent cytoskeletally associated Lgl. Lgl specifically regulates internalization of Sanpodo, likely through endocytosis, but is not required for the endocytosis Delta, which is a required step in the Notch-mediated cell fate decision during asymmetric cell division. Conversely, the E3 ubiquitin ligase neuralized is required for both Delta endocytosis and the internalization of Sanpodo. This study identifies a hitherto unreported role for Lgl as a regulator of Sanpodo during asymmetric cell division in the adult PNS.