PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody
doi: 10.1038/ncb2036
pmid: 20208530
PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody
Several subunits of the class III phosphatidylinositol-3-OH kinase (PI(3)K-III) complex are known as tumour suppressors. Here we uncover a function for this complex and its catalytic product phosphatidylinositol-3-phosphate (PtdIns(3)P) in cytokinesis. We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis. Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A. Depletion of the VPS34 or Beclin 1 subunits of PI(3)K-III causes cytokinesis arrest and an increased number of binucleate and multinucleate cells, in a similar manner to the depletion of FYVE-CENT, KIF13A or TTC19. These results provide a mechanism for the translocation and docking of a cytokinesis regulatory machinery at the midbody.
- University of Oslo Norway
- Oslo University Hospital Norway
Centrosome, Endosomal Sorting Complexes Required for Transport, Cell Cycle, Kinesins, Membrane Proteins, Mitosis, Biosensing Techniques, Mice, Phosphatidylinositol 3-Kinases, Microscopy, Fluorescence, Mutation, Animals, Drosophila Proteins, Humans, Beclin-1, Drosophila, Apoptosis Regulatory Proteins, Carrier Proteins, Cytokinesis, HeLa Cells
Centrosome, Endosomal Sorting Complexes Required for Transport, Cell Cycle, Kinesins, Membrane Proteins, Mitosis, Biosensing Techniques, Mice, Phosphatidylinositol 3-Kinases, Microscopy, Fluorescence, Mutation, Animals, Drosophila Proteins, Humans, Beclin-1, Drosophila, Apoptosis Regulatory Proteins, Carrier Proteins, Cytokinesis, HeLa Cells
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