Lgl resets Par complex membrane loading at mitotic exit to enable asymmetric neural stem cell division.

The Par complex regulates cell polarity in diverse animal cells (1-4) , 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 Drosophila 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(5). 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.