An essential function of the C. elegans ortholog of TPX2 is to localize activated aurora A kinase to mitotic spindles

Dev Cell. 2005 Aug;9(2):237-48. doi: 10.1016/j.devcel.2005.07.002.

Abstract

In vertebrates, the microtubule binding protein TPX2 is required for meiotic and mitotic spindle assembly. TPX2 is also known to bind to and activate Aurora A kinase and target it to the spindle. However, the relationship between the TPX2-Aurora A interaction and the role of TPX2 in spindle assembly is unclear. Here, we identify TPXL-1, a C. elegans protein that is the first characterized invertebrate ortholog of TPX2. We demonstrate that an essential role of TPXL-1 during mitosis is to activate and target Aurora A to microtubules. Our data suggest that this targeting stabilizes microtubules connecting kinetochores to the spindle poles. Thus, activation and targeting of Aurora A appears to be an ancient and conserved function of TPX2 that plays a central role in mitotic spindle assembly.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinases
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Embryo, Nonmammalian / physiology
  • Enzyme Activation
  • Humans
  • Kinetochores / physiology
  • Microtubule-Associated Proteins / genetics
  • Microtubules / physiology*
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / genetics
  • Phosphoproteins / genetics
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases
  • Sequence Homology, Amino Acid
  • Spindle Apparatus / genetics
  • Spindle Apparatus / physiology*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • TPX2 protein, human
  • TPXL-1 protein, C elegans
  • Xenopus Proteins
  • Protein Kinases
  • AURKA protein, Xenopus
  • Aurora Kinases
  • Protein Serine-Threonine Kinases