Cell cycle-regulated membrane binding of NuMA contributes to efficient anaphase chromosome separation

Zhen Zheng, Qingwen Wan, Gerry Meixiong, Quansheng Du

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Accurate and efficient separation of sister chromatids during anaphase is critical for faithful cell division. It has been proposed that cortical dynein-generated pulling forces on astral microtubules contribute to anaphase spindle elongation and chromosome separa tion. In mammalian cells, however, definitive evidence for the involvement of cortical dynein in chromosome separation is missing. It is believed that dynein is recruited and anchored at the cell cortex during mitosis by the α subunit of heterotrimeric G protein (Gα)/mammalian homologue of Drosophila Partner of Inscuteable/nuclear mitotic apparatus (NuMA) ternary complex. Here we uncover a Gα/LGN-independent lipid- and membrane-binding domain at the C-terminus of NuMA. We show that the membrane binding of NuMA is cell cycle regulat ed - it is inhibited during prophase and metaphase by cyclin-dependent kinase 1 (CDK1)- mediated phosphorylation and only occurs after anaphase onset when CDK1 activity is down- regulated. Further studies indicate that cell cycle-regulated membrane association of NuMA underlies anaphase-specific enhancement of cortical NuMA and dynein. By replacing endog enous NuMA with membrane-binding-deficient NuMA, we can specifically reduce the cortical accumulation of NuMA and dynein during anaphase and demonstrate that cortical NuMA and dynein contribute to efficient chromosome separation in mammalian cells.

Original languageEnglish (US)
Pages (from-to)606-619
Number of pages14
JournalMolecular Biology of the Cell
Volume25
Issue number5
DOIs
StatePublished - Mar 1 2014

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Anaphase
Spindle Apparatus
Nuclear Envelope
Dyneins
Cell Cycle
Chromosomes
CDC2 Protein Kinase
Heterotrimeric GTP-Binding Proteins
Prophase
Chromatids
Metaphase
Membrane Lipids
Mitosis
Microtubules
Cell Division
Drosophila
Phosphorylation
Membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cell cycle-regulated membrane binding of NuMA contributes to efficient anaphase chromosome separation. / Zheng, Zhen; Wan, Qingwen; Meixiong, Gerry; Du, Quansheng.

In: Molecular Biology of the Cell, Vol. 25, No. 5, 01.03.2014, p. 606-619.

Research output: Contribution to journalArticle

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