Human chromokinesin KIF4A functions in chromosome condensation and segregation.
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.
National Cancer Institute, National Institutes of Health, Bldg. 41, Rm. B 507, 41 Library Dr., Bethesda, MD 20892, USA. mazumdam@mail.nih.gov
Manjari
M
Mazumdar
Suma
S
Sundareshan
Tom
T
Misteli
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000782:Aneuploidy; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D020090:Chromosome Segregation / Q000502:physiology*; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000502:physiology*; D008677:Metaphase / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D034622:RNA Interference; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
D004268:DNA-Binding Proteins; D020409:Molecular Motor Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; D000251:Adenosine Triphosphatases; C484228:KIF4A protein, human; C484229:KIF4B protein, human; D016547:Kinesins