Art of Dividing: Researchers Decode Function and Protein Content of the Centrosome
ScienceDaily (Sep. 2, 2010) — A basic requirement for growth and life of a multicellular organism is the ability of its cells to divide. Chromosomes in the cells duplicate and are then distributed among the daughter cells. This distribution is organized by a protein complex made up of several hundred different proteins, called the centrosome. In cancer cells, the centrosome often assumes an unnatural shape or is present in uncontrolled numbers. The reasons for this were previously largely unknown.
(A) During cell division, chromosomes (red) are distributed evenly by thread-like structures (microtubules) emanating from the centrosome (green). (B) Inactivation of a centrosomal protein causes abnormal organisation of the mitotic spindle microtubules and a faulty distribution of chromosomes. © MPI for Molecular Genetics / B. Lange
Scientists at the Max Planck Institute for Molecular Genetics in Berlin, together with colleagues at the German Cancer Research Center in Heidelberg and at the Leibniz Institute for Age Research -- Fritz Lipmann Institute in Jena, have investigated the functions of the different centrosomal components. The researchers led by Bodo Lange now present their results in theEMBO Journal, detailing the centrosome's components and their functions. Their work extends our knowledge of regulation of cell division and opens the door to new investigations into cancer development.
As part of their research, the scientists examined centrosomes of the fruit fly Drosophila as well as those from human cells. "The fruit fly is a terrific system for investigating the centrosome, because the basic mechanisms of cell division are very similar between fly and human," Bodo Lange, the research group leader, explains.
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The EMBO Journal advance online publication 3 September 2010;doi:10.1038/emboj.2010.210
Subject Categories:
Cell and Tissue Architecture | Cell Cycle
Proteomic and functional analysis of the mitoticDrosophila centrosome
Hannah Müller1,4, David Schmidt2,4, Sandra Steinbrink3,4, Ekaterina Mirgorodskaya1,4, Verena Lehmann1, Karin Habermann1, Felix Dreher1, Niklas Gustavsson1,5, Thomas Kessler1, Hans Lehrach1, Ralf Herwig1, Johan Gobom1, Aspasia Ploubidou2, Michael Boutros3 and Bodo M H Lange1
Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, Berlin, Germany
Leibniz Institute for Age Research—Fritz Lipmann Institute, Jena, Germany
German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and University of Heidelberg, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany
Correspondence to:
Bodo M H Lange, Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, Ihnestr. 73, Berlin 14195, Germany. Tel.: +49 308 413 1645; Fax: +49 308 413 1128; E-mail: lange_b@molgen.mpg.de
4These authors contributed equally to this work
5Present address: Novozymes Biopharma AB, Lund 22009, Sweden
Received 9 February 2010; Accepted 4 August 2010
Regulation of centrosome structure, duplication and segregation is integrated into cellular pathways that control cell cycle progression and growth. As part of these pathways, numerous proteins with well-established non-centrosomal localization and function associate with the centrosome to fulfill regulatory functions. In turn, classical centrosomal components take up functional and structural roles as part of other cellular organelles and compartments. Thus, although a comprehensive inventory of centrosome components is missing, emerging evidence indicates that its molecular composition reflects the complexity of its functions. We analysed the Drosophila embryonic centrosomal proteome using immunoisolation in combination with mass spectrometry. The 251 identified components were functionally characterized by RNA interference. Among those, a core group of 11 proteins was critical for centrosome structure maintenance. Depletion of any of these proteins in Drosophila SL2 cells resulted in centrosome disintegration, revealing a molecular dependency of centrosome structure on components of the protein translation machinery, actin- and RNA-binding proteins. In total, we assigned novel centrosome-related functions to 24 proteins and confirmed 13 of these in human cells.
Keywords: cell cycle, centrosome, Drosophila, mitosis, proteomics
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