The ability of Slik to phosphorylate moesin in discs depends on PP2A_STRIPAK. (A–C) Wing discs overexpressing Slik alone (A) or together with dsRNA targeting Strip (B) or Cka (C) in a stripe of cells under control of the ptc-GAL4 driver. Discs were stained with antibody against p-moesin. Images are maximum projections of 56–66 confocal sections spanning the entire thickness of the disc. Arrow indicates upregulation of p-moesin levels in Slik-overexpressing cells. (D) Quantification of p-moesin fluorescence intensity in cells in the ptc stripe normalized to wild-type posterior compartment cells in discs of the genotypes in A–C. Measurements were made in 7 wing discs for each genotype. Two-tailed unpaired t test with P value: ***, P < 0.0001. (E) Model for the regulation of Slik localization at the cell cortex (adapted from Pelaseyed et al., 2017). Cycle of phosphorylation/dephosphorylation of Slik serves as an electrostatic switch that controls Slik cortical association. (a) Phosphorylated Slik is localized in the cytoplasm due to electrostatic repulsion with the negatively charged plasma membrane. (b) dSTRIPAK phosphatase activity (PP2A_STRIPAK) dephosphorylates Slik and promotes its association with the cortex. (c) The poly-basic CTD is responsible for Slik localization at the cortex through electrostatic interaction. (d) Once at the cell cortex, Slik can phosphorylate the PtdIns(4,5)P₂-primed moesin on its T559. (e) Activated moesin is essential for proper mitotic morphogenesis and epithelial integrity.