ch-TOGp is required for microtubule aster formation in a mammalian mitotic extract

J Biol Chem. 2000 Apr 21;275(16):12346-52. doi: 10.1074/jbc.275.16.12346.

Abstract

Microtubules induced to polymerize with taxol in a mammalian mitotic extract organize into aster-like arrays in a centrosome-independent process that is driven by microtubule motors and structural proteins. These microtubule asters accurately reflect the noncentrosomal aspects of mitotic spindle pole formation. We show here that colonic-hepatic tumor-overexpressed gene (ch-TOGp) is an abundant component of these asters. We have prepared ch-TOGp-specific antibodies and show by immunodepletion that ch-TOGp is required for microtubule aster assembly. Microtubule polymerization is severely inhibited in the absence of ch-TOGp, and silver stain analysis of the ch-TOGp immunoprecipitate indicates that it is not present in a preformed complex and is the only protein removed from the extract during immunodepletion. Furthermore, the reduction in microtubule polymerization efficiency in the absence of ch-TOGp is dependent on ATP. These results demonstrate that ch-TOGp is a major constituent of microtubule asters assembled in a mammalian mitotic extract and that it is required for robust microtubule polymerization in an ATP-dependent manner in this system even though taxol is present. These data, coupled with biochemical and genetic data derived from analysis of ch-TOGp-related proteins in other organisms, indicate that ch-TOGp is a key factor regulating microtubule dynamics during mitosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Electrophoresis, Polyacrylamide Gel
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / physiology*
  • Molecular Sequence Data
  • Molecular Weight
  • Polymers / metabolism
  • Spindle Apparatus / physiology*

Substances

  • CKAP5 protein, human
  • Microtubule-Associated Proteins
  • Polymers