Formation of Spindle Poles by Dynein/Dynactin-dependent Transport of NuMA

doi:10.1083/jcb.149.4.851

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© The Rockefeller University Press, 0021-9525/2000/5/851/ $5.00
The Journal of Cell Biology, Volume 149, Number 4, May 15, 2000 851-862

Original Article

Formation of Spindle Poles by Dynein/Dynactin-dependent Transport of NuMA

Andreas Merdes^a, Rebecca Heald^b, Kumiko Samejima^a, William C. Earnshaw^a, and Don W. Cleveland^c
^a ICMB, University of Edinburgh, Edinburgh EH9 3JR, Scotland
^b Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California 94720
^c Ludwig Institute for Cancer Research and Division of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093-0660

Correspondence to: Andreas Merdes, ICMB, University of Edinburgh, King's Buildings, Edinburgh EH9 3JR, Scotland, UK. Tel:011 44 131 650 7075 Fax:011 44 131 650 7360 E-mail:a.merdes{at}ed.ac.uk.

NuMA is a large nuclear protein whose relocation to the spindlepoles is required for bipolar mitotic spindle assembly. We showhere that this process depends on directed NuMA transport towardmicrotubule minus ends powered by cytoplasmic dynein and itsactivator dynactin. Upon nuclear envelope breakdown, large cytoplasmicaggregates of green fluorescent protein (GFP)-tagged NuMA streampoleward along spindle fibers in association with the actin-relatedprotein 1 (Arp1) protein of the dynactin complex and cytoplasmicdynein. Immunoprecipitations and gel filtration demonstratethe assembly of a reversible, mitosis-spe-cific complex of NuMAwith dynein and dynactin. NuMA transport is required for spindlepole assembly and maintenance, since disruption of the dynactincomplex (by increasing the amount of the dynamitin subunit)or dynein function (with an antibody) strongly inhibits NuMAtranslocation and accumulation and disrupts spindle pole assembly.

Key Words: mitosis, microtubules, motor proteins, centrosome, spindle polematrix

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