β-catenin asymmetry is regulated by PLA1 and retrograde traffic in C-elegans stem cell divisions
β-catenin asymmetry is regulated by PLA1 and retrograde traffic in C-elegans stem cell divisions
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DOI：
10.1038/emboj.2008.102
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发表时间：
2008-06-18
期刊：
影响因子：
11.4
通讯作者：
Arai, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kanamori, Takahiro;Inoue, Takao;Arai, Hiroyuki
不对称分裂是干细胞的一个重要特性。在秀丽隐杆线虫中，Wnt/β-连环蛋白不对称通路决定了大多数不对称分裂的极性。 Wnt 信号传导成分（例如 β-连环蛋白）不对称地定位于母细胞的皮质，以产生两个不同的子细胞。然而，使它们极化的分子机制仍有待阐明。在这里，我们证明细胞内磷脂酶 A(1) (PLA(1))（一种特征尚不明确的脂质代谢酶）控制着上皮干细胞（接缝细胞）末端不对称分裂中 β-连环蛋白的亚细胞定位。在 ipla-1（单个线虫 PLA(1) 基因）的突变体中，皮质 β-连环蛋白被离域，细胞命运规范的不对称性在不对称分裂中被破坏。 ipla-1突变表型通过在seam细胞中以催化活性依赖的方式表达ipla-1来挽救。此外，我们利用 ipla-1 突变体的遗传筛选表明，seam 细胞中内体到高尔基体逆行转运的减少恢复了 β-连环蛋白对 ipla-1 突变体的正常亚细胞定位。我们提出 ipla-1 调节的膜运输提供了一种控制 β-catenin 皮质不对称性的机制。
Asymmetric division is an important property of stem cells. In Caenorhabditis elegans, the Wnt/beta-catenin asymmetry pathway determines the polarity of most asymmetric divisions. The Wnt signalling components such as beta-catenin localize asymmetrically to the cortex of mother cells to produce two distinct daughter cells. However, the molecular mechanism to polarize them remains to be elucidated. Here, we demonstrate that intracellular phospholipase A(1) (PLA(1)), a poorly characterized lipid-metabolizing enzyme, controls the subcellular localizations of beta-catenin in the terminal asymmetric divisions of epithelial stem cells (seam cells). In mutants of ipla-1, a single C. elegans PLA(1) gene, cortical beta-catenin is delocalized and the asymmetry of cell-fate specification is disrupted in the asymmetric divisions. ipla-1 mutant phenotypes are rescued by expression of ipla-1 in seam cells in a catalytic activity-dependent manner. Furthermore, our genetic screen utilizing ipla-1 mutants reveals that reduction of endosome-to-Golgi retrograde transport in seam cells restores normal subcellular localization of beta-catenin to ipla-1 mutants. We propose that membrane trafficking regulated by ipla-1 provides a mechanism to control the cortical asymmetry of beta-catenin.