The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells

  1. Fanni Gergely1,
  2. Viji M. Draviam2,4, and
  3. Jordan W. Raff3,5
  1. 1Department of Pharmacology, 2Department of Zoology, and 3Department of Genetics, University of Cambridge, Wellcome Trust/Cancer Research UK Institute, Cambridge CB2 1QR, UK

Abstract

The ch-TOG/XMAP215 family of proteins bind directly to microtubules and appear to play an essential role in stabilizing spindle microtubules. These proteins stabilize microtubules mainly by influencing microtubule plus-end dynamics, yet, in vivo, they are all strongly concentrated at spindle poles, where the minus ends of the microtubules are concentrated. In Drosophila embryos, the centrosomal protein D-TACC is required to efficiently recruit ch-TOG/Msps to centrosomes. In humans, ch-TOG and the three known TACC proteins have been implicated in cancer, but their functions are unknown. Here we extensively depleted TACC3 and ch-TOG from HeLa cells using RNA interference. In TACC3-depleted cells, spindles are well organized, but microtubules are partially destabilized and ch-TOG is no longer concentrated on spindle microtubules. In ch-TOG-depleted cells, relatively robust spindles form, but the spindles are highly disorganized. Thus, in human somatic cells, ch-TOG appears to play a major role in organizing spindle poles, and a more minor role in stabilizing spindle microtubules that is, at least in part, mediated via an interaction with TACC3.

Keywords

Footnotes

  • 4 Present address: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

  • 5 Corresponding author.

  • E-MAIL j.raff{at}welc.cam.ac.uk; FAX 44-1223-334089.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.245603.

    • Received August 7, 2002.
    • Accepted November 4, 2002.
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