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Published online 23 August 2004. doi:10.1083/jcb.200401142
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 5, 613-620
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 Human chromokinesin KIF4A functions in chromosome condensation and segregation

Manjari Mazumdar1, Suma Sundareshan2, and Tom Misteli1

1 National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
2 Bangalore Genei Pvt. Ltd, BDA Industrial Suburb, Peenya, Bangalore 560058 India

Address correspondence to Manjari Mazumdar, National Cancer Institute, National Institutes of Health, Bldg. 41, Rm. B 507, 41 Library Dr., Bethesda, MD 20892. Tel.: (301) 435-2672. Fax: (301) 496-4951. email: mazumdam{at}mail.nih.gov


Abstract
Accurate chromosome alignment at metaphase and subsequent segregation of condensed chromosomes is a complex process involving elaborate and only partially characterized molecular machinery. Although several spindle associated molecular motors have been shown to be essential for mitotic function, only a few chromosome arm–associated motors have been described. Here, we show that human chromokinesin human HKIF4A (HKIF4A) is an essential chromosome-associated molecular motor involved in faithful chromosome segregation. HKIF4A localizes in the nucleoplasm during interphase and on condensed chromosome arms during mitosis. It accumulates in the mid-zone from late anaphase and localizes to the cytokinetic ring during cytokinesis. RNA interference–mediated depletion of HKIF4A in human cells results in defective prometaphase organization, chromosome mis-alignment at metaphase, spindle defects, and chromosome mis-segregation. HKIF4A interacts with the condensin I and II complexes and HKIF4A depletion results in chromosome hypercondensation, suggesting that HKIF4A is required for maintaining normal chromosome architecture. Our results provide functional evidence that human KIF4A is a novel component of the chromosome condensation and segregation machinery functioning in multiple steps of mitotic division.

Key Words: chromokinesin; spindle; chromosome condensation; molecular motor

Abbreviations used in this paper: HKIF4A, human KIF4A; MT, microtubule; RNAi, RNA interference.


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