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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2008     Display Documents

ID: 414307.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2008
The Mammalian SPD-2 Ortholog Cep192 Regulates Centrosome Biogenesis
Authors:Zhu, Fei; Lawo, Steffen; Bird, Alex; Pinchev, Deborah; Ralph, Alison; Richter, Constance; Müller-Reichert, Thomas; Kittler, Ralf; Hyman, Anthony A; Pelletier, Laurence
Date of Publication (YYYY-MM-DD):2008
Title of Journal:Current Biology
Issue / Number:2
Start Page:136
End Page:141
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Centrosomes are the major microtubule-organizing centers of mammalian cells. They are composed of a centriole pair and surrounding microtubule-nucleating material termed pericentriolar material (PCM) [1]. Bipolar mitotic spindle assembly relies on two intertwined processes: centriole duplication and centrosome maturation. In the first process, the single interphase centrosome duplicates in a tightly regulated manner so that two centrosomes are present in mitosis [2, 3]. In the second process, the two centrosomes increase in size and microtubule nucleation capacity through PCM recruitment, a process referred to as centrosome maturation [4]. Failure to properly orchestrate centrosome duplication and maturation is inevitably linked to spindle defects, which can result in aneuploidy and promote cancer progression [5]. It has been proposed that centriole assembly during duplication relies on both PCM and centriole proteins, raising the possibility that centriole duplication depends on PCM recruitment [6]. In support of this model, C. elegans SPD-2 and mammalian NEDD-1 (GCP-WD) are key regulators of both these processes [7-13]. SPD-2 protein sequence homologs have been identified in flies, mice, and humans, but their roles in centrosome biogenesis until now have remained unclear [10, 14-16]. Here, we show that Cep192, the human homolog of C. elegans and D. melanogaster SPD-2, is a major regulator of PCM recruitment, centrosome maturation, and centriole duplication in mammalian cells. We propose a model in which Cep192 and Pericentrin are mutually dependent for their localization to mitotic centrosomes during centrosome maturation. Both proteins are then required for NEDD-1 recruitment and the subsequent assembly of gamma-TuRCs and other factors into fully functional centrosomes.
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI f�r molekulare Zellbiologie und Genetik
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