LaFoya Bryce, Welch Sarah E, Prehoda Kenneth E
Institute of Molecular Biology, Department of Chemistry and Biochemistry, 1229 University of Oregon, Eugene, OR 97403.
bioRxiv. 2024 Dec 2:2024.09.29.615680. doi: 10.1101/2024.09.29.615680.
The Par complex regulates cell polarity in diverse animal cells , but how its localization is restricted to a specific membrane domain remains unclear. We investigated how the tumor suppressor Lethal giant larvae (Lgl) polarizes the Par complex in neural stem cells (NSCs or neuroblasts). In contrast to epithelial cells, where Lgl and the Par complex occupy mutually exclusive membrane domains, Lgl is cytoplasmic when the Par complex is apically polarized in NSCs. Importantly, we found that Lgl's key function is not in directly regulating metaphase Par polarity, but rather in removing the Par complex from the membrane at the end of mitosis, creating a "polarity reset" for the next cell cycle. Without this Lgl-mediated reset, we found that residual Par complex remains on the basal membrane during subsequent divisions, disrupting fate determinant polarization and proper asymmetric cell division. These findings reveal a novel mechanism of polarity regulation by Lgl and highlight the importance of the prepolarized state in Par-mediated polarity.
Par复合物在多种动物细胞中调节细胞极性，但其定位如何局限于特定膜结构域仍不清楚。我们研究了肿瘤抑制因子致死性巨幼虫（Lgl）如何在神经干细胞（NSCs或神经母细胞）中使Par复合物极化。与上皮细胞不同，在NSCs中，当Par复合物顶端极化时，Lgl和Par复合物占据相互排斥的膜结构域，而Lgl位于细胞质中。重要的是，我们发现Lgl的关键功能不是直接调节中期Par极性，而是在有丝分裂末期将Par复合物从膜上移除，为下一个细胞周期创造一个“极性重置”。没有这种Lgl介导的重置，我们发现残余的Par复合物在随后的分裂过程中仍留在基底膜上，破坏命运决定因子的极化和正确的不对称细胞分裂。这些发现揭示了Lgl调节极性的新机制，并突出了预极化状态在Par介导的极性中的重要性。
