PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody.

Article Details

Citation

Sagona AP, Nezis IP, Pedersen NM, Liestol K, Poulton J, Rusten TE, Skotheim RI, Raiborg C, Stenmark H

PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody.

Nat Cell Biol. 2010 Apr;12(4):362-71. doi: 10.1038/ncb2036. Epub 2010 Mar 7.

PubMed ID
20208530 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Phosphatidylinositol 3-kinase catalytic subunit type 3Q8NEB9Details
Beclin-1Q14457Details