Human Cep192 Is Required for Mitotic Centrosome and Spindle Assembly

Maria Ana Gomez-Ferreria, Uttama Rath, Daniel W. Buster, Sumit K. Chanda, Jeremy S. Caldwell, Daniel R. Rines, David J. Sharp

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

As cells enter mitosis, centrosomes dramatically increase in size and ability to nucleate microtubules. This process, termed centrosome maturation, is driven by the accumulation and activation of γ-tubulin and other proteins that form the pericentriolar material on centrosomes during G2/prophase. Here, we show that the human centrosomal protein, Cep192 (centrosomal protein of 192 kDa), is an essential component of the maturation machinery. Specifically, we have found that siRNA depletion of Cep192 results in a complete loss of functional centrosomes in mitotic but not interphase cells. In mitotic cells lacking Cep192, microtubules become organized around chromosomes but rarely acquire stable bipolar configurations. These cells contain normal numbers of centrioles but cannot assemble γ-tubulin, pericentrin, or other pericentriolar proteins into an organized PCM. Alternatively, overexpression of Cep192 results in the formation of multiple, extracentriolar foci of γ-tubulin and pericentrin. Together, our findings support the hypothesis that Cep192 stimulates the formation of the scaffolding upon which γ-tubulin ring complexes and other proteins involved in microtubule nucleation and spindle assembly become functional during mitosis.

Original languageEnglish (US)
Pages (from-to)1960-1966
Number of pages7
JournalCurrent Biology
Volume17
Issue number22
DOIs
StatePublished - Nov 20 2007

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Gomez-Ferreria, M. A., Rath, U., Buster, D. W., Chanda, S. K., Caldwell, J. S., Rines, D. R., & Sharp, D. J. (2007). Human Cep192 Is Required for Mitotic Centrosome and Spindle Assembly. Current Biology, 17(22), 1960-1966. https://doi.org/10.1016/j.cub.2007.10.019