PP1-Mediated Dephosphorylation of Lgl Controls Apical-basal Polarity

Apical-basal polarity is a common trait that underlies epithelial function. Although the asymmetric distribution of cortical polarity proteins works in a functioning equilibrium, it also retains plasticity to accommodate cell division, during which the basolateral determinant Lgl is released from the cortex. Here, we investigated how Lgl restores its cortical localization to maintain the integrity of dividing epithelia. We show that cytoplasmic Lgl is reloaded to the cortex at mitotic exit in Drosophila epithelia. Lgl cortical localization depends on protein phosphatase 1, which dephosphorylates Lgl on the serines phosphorylated by aPKC and Aurora A kinases through a mechanism that relies on the regulatory subunit Sds22 and a PP1-interacting RVxF motif of Lgl. This mechanism maintains epithelial polarity and is of particular importance at mitotic exit to couple Lgl cortical reloading with the polarization of the apical domain. Hence, PP1-mediated dephosphorylation of Lgl preserves the apicalbasal organization of proliferative epithelia. We thank Daniel St Johnston, François Schweisguth, Guilles Hickson, Jürgen Knoblich, Torcato Martins, Yang Hong, and the Bloomington Drosophila Stock Center for providing plasmids and fly stocks. This work was funded by national funds through Fundação para a Ciência e a Tecnologia (FCT) under project PTDC/BEX-BCM/0432/2014 . This work has also received funding from the project Norte-01-0145-FEDER-000029 , supported by Norte Portugal Regional Operational Program (NORTE 2020). E.M. holds an FCT Investigator position. S.M. and M.G. are supported by FCT PhD grants. M.O. is supported by a fellowship from FCT and the GABBA PhD program from the University of Porto .