FIP5 phosphorylation during mitosis regulates apical trafficking and lumenogenesis

Synopsis image This study shows that epithelial lumen formation is regulated by FIP5 phosphorylation, which inhibits its interaction with SNX18 during metaphase and anaphase, ensuring that the transport of apical endocytic carriers happens only after the formation of the AMIS. FIP5-endosomes travel along the central spindle to the apical membrane initiation site (AMIS). FIP5-T276 phosphorylation by GSK-3 regulates the timing of apical lumen formation. The midbody formation during cytokinesis is a symmetry-breaking event leading to the establishment of a single apical lumen site. Abstract Apical lumen formation is a key step during epithelial morphogenesis. The establishment of the apical lumen is a complex process that involves coordinated changes in plasma membrane composition, endocytic transport, and cytoskeleton organization. These changes are accomplished, at least in part, by the targeting and fusion of Rab11/FIP5-containing apical endosomes with the apical membrane initiation site (AMIS). Although AMIS formation and polarized transport of Rab11/FIP5-containing endosomes are crucial for the formation of a single apical lumen, the spatiotemporal regulation of this process remains poorly understood. Here, we demonstrate that the formation of the midbody during cytokinesis is a symmetry-breaking event that establishes the location of the AMIS. The interaction of FIP5 with SNX18, which is required for the formation of apical endocytic carriers, is inhibited by GSK-3 phosphorylation at FIP5-T276. Importantly, we show that FIP5-T276 phosphorylation occurs specifically during metaphase and anaphase, to ensure the fidelity and timing of FIP5-endosome targeting to the AMIS during apical lumen formation.