Extracellular control of PAR protein localization during asymmetric cell division in the C. elegans embryo

Extracellular control of PAR protein localization during asymmetric cell division in the C. elegans embryo
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DOI:
10.1242/dev.054742
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发表时间:
2010-10-01
期刊:
影响因子:
4.6
通讯作者:
Sawa, Hitoshi
Sawa, Hitoshi
中科院分区:
生物学2区
文献类型:
--
作者:
Arata, Yukinobu;Lee, Jen-Yi;Sawa, Hitoshi

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控制不对称细胞分裂的轴以确定动物发育期间分化细胞的未来位置。PAR蛋白在果蝇成神经细胞和C. elegans胚胎与胚胎的轴对齐。然而,无论是细胞外或细胞内的信号决定的定位PAR蛋白的方向仍然存在争议。In C.在线虫中,P0合子和生殖细胞(P1、P2和P3)经历一系列不对称细胞分裂。有趣的是,P0和P1分区的轴与P2和P3分区的轴相反。环指蛋白PAR-2和激酶PAR-1在与内胚层前体接触的部位重新定位于P2和P3种系前体的前侧。使用体外方法,我们已经发现,PAR-2蛋白是不对称分布的细胞外信号的情况下,但在P2和P3细胞中的蛋白定位的方向是由与内胚层前体细胞接触。我们的突变体分析表明,MES-1和src-1,分别编码一个跨膜蛋白和酪氨酸激酶,不需要建立PAR-2的不对称分布,但需要确定其方向的网站与内胚层前体接触。在不对称P2和P3分裂期间,PAR-2定位通过MES-1/SRC-1信号传导由细胞外信号控制。我们的研究结果表明,Src的功能作为一个进化上保守的分子链接,协调外部线索与PAR蛋白定位。
The axis of asymmetric cell division is controlled to determine the future position of differentiated cells during animal development. The asymmetric localization of PAR proteins in the Drosophila neuroblast and C. elegans embryo are aligned with the axes of the embryo. However, whether extracellular or intracellular signals determine the orientation of the localization of PAR proteins remains controversial. In C. elegans, the P0 zygote and germline cells (P1, P2, and P3) undergo a series of asymmetric cell divisions. Interestingly, the axis of the P0 and P1 divisions is opposite to that of the P2 and P3 divisions. PAR-2, a ring-finger protein, and PAR-1, a kinase, relocalize to the anterior side of the P2 and P3 germline precursors at the site of contact with endodermal precursors. Using an in vitro method, we have found that the PAR-2 protein is distributed asymmetrically in the absence of extracellular signals, but the orientation of the protein localization in the P2 and P3 cells is determined by contact with endodermal precursor cells. Our mutant analyses suggest that mes-1 and src-1, which respectively encode a transmembrane protein and a tyrosine kinase, were not required to establish the asymmetric distribution of PAR-2, but were required to determine its orientation at the site of contact with the endodermal precursors. The PAR-2 localization during the asymmetric P2 and P3 divisions is controlled by extracellular signals via MES-1/SRC-1 signaling. Our findings suggest that Src functions as an evolutionarily conserved molecular link that coordinates extrinsic cues with PAR protein localization.