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Vol. 12, Issue 9, 2776-2789, September 2001
and
*Division Molecular Medicine, Wadsworth Center, New York State
Department of Health, Albany, New York 12201-0509;
CENP-E is a kinesin-like protein that when depleted from mammalian
kinetochores leads to mitotic arrest with a mixture of aligned and unaligned chromosomes. In the present study, we used immunofluorescence, video, and electron microscopy to demonstrate that
depletion of CENP-E from kinetochores via antibody
microinjection reduces kinetochore microtubule binding by
23% at aligned chromosomes, and severely reduces microtubule binding
at unaligned chromosomes. Disruption of CENP-E function also reduces
tension across the centromere, increases the incidence of spindle pole
fragmentation, and results in monooriented chromosomes approaching
abnormally close to the spindle pole. Nevertheless, chromosomes show
typical patterns of congression, fast poleward motion, and oscillatory motions. Furthermore, kinetochores of aligned and unaligned
chromosomes exhibit normal patterns of checkpoint protein localization.
These data are explained by a model in which redundant mechanisms
enable kinetochore microtubule binding and checkpoint
monitoring in the absence of CENP-E at kinetochores, but
where reduced microtubule-binding efficiency, exacerbated by poor
positioning at the spindle poles, results in chronically monooriented
chromosomes and mitotic arrest. Chromosome position within the spindle
appears to be a critical determinant of CENP-E function at kinetochores.
Department of Biomedical Science, State University of
New, York, Albany, New York 12222; §Institute Cancer
Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111;
and Siena College, Loudonville, New York 12211
Corresponding author. E-mail
address: bruce.mcewen{at}wadsworth.org.
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