FIP5 phosphorylation during mitosis regulates apical trafficking and lumenogenesis

EMBO Rep. 2014 Apr;15(4):428-37. doi: 10.1002/embr.201338128. Epub 2014 Mar 3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Membrane / metabolism
  • Cell Polarity
  • Cytokinesis
  • Dogs
  • HeLa Cells
  • Humans
  • Madin Darby Canine Kidney Cells
  • Mitosis*
  • Phosphorylation
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Protein Transport

Substances

  • Adaptor Proteins, Signal Transducing
  • RAB11FIP5 protein, human