title: FIP5 phosphorylation during mitosis regulates apical trafficking and lumenogenesis.
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.
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, Anschutz Medical Campus University of Colorado Denver, Aurora, CO, USA.
authors.forename: Dongying
authors.initials: D
authors.lastname: Li
authors.forename: Anthony
authors.initials: A
authors.lastname: Mangan
authors.forename: Louis
authors.initials: L
authors.lastname: Cicchini
authors.forename: Ben
authors.initials: B
authors.lastname: Margolis
authors.forename: Rytis
authors.initials: R
authors.lastname: Prekeris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D048749:Cytokinesis; D004285:Dogs; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008938:Mitosis; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485422:RAB11FIP5 protein, human