Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N-0310 Oslo, Norway.
Nat Cell Biol. 2010 Apr;12(4):362-71. doi: 10.1038/ncb2036. Epub 2010 Mar 7.
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.
几种 III 类磷脂酰肌醇-3-羟基激酶（PI(3)K-III）复合物亚基被认为是肿瘤抑制因子。在这里，我们揭示了该复合物及其催化产物磷脂酰肌醇-3-磷酸（PtdIns(3)P）在胞质分裂中的功能。我们表明，PtdIns(3)P 在胞质分裂期间定位于中体，并招募中心体蛋白 FYVE-CENT（ZFYVE26）及其结合伙伴 TTC19，后者反过来与 CHMP4B 相互作用，CHMP4B 是参与胞质分裂分离步骤的内体分选复合物所需的运输（ESCRT）-III 亚基。FYVE-CENT 和 TTC19 从中心体向中体的易位需要另一种 FYVE-CENT 相互作用蛋白，微管马达 KIF13A。VPS34 或 Beclin 1 亚基的 PI(3)K-III 的耗竭会导致胞质分裂停滞，并增加双核和多核细胞的数量，这与 FYVE-CENT、KIF13A 或 TTC19 的耗竭相似。这些结果为在中体处易位和对接细胞分裂调节机制提供了一种机制。
