Consequences of Numerical Centrosome Defects in Development and Disease
Defects in centrosome number or structure can have considerable consequences for the physiology of an organism. Aberrant centrosome number has been proposed for a century to contribute to genome instability and tumour formation. However, in the last decad
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Consequences of Numerical Centrosome Defects in Development and Disease Davide Gambarotto and Renata Basto
Abstract
Defects in centrosome number or structure can have considerable consequences for the physiology of an organism. Aberrant centrosome number has been proposed for a century to contribute to genome instability and tumour formation. However, in the last decade, mutations in centrosome genes have been described in diseases characterised by defective growth. Centrosome dysfunction can therefore have opposite effects on the homeostasis of the organism. Here we discuss how deregulation of centrosome number during embryonic development might contribute to growth defective syndromes such as autosomal recessive primary microcephaly (MCPH) and primordial dwarfism. We further discuss how the same defects might play a role in cancer when present in adult tissues.
5.1
Introduction
The centrosome is the major microtubule-organising centre of animal cells (Kellogg et al. 1994). It participates in different processes such as cell division, motility and polarity, mainly by organising the microtubule network. Centrosomes are not present in plants, whereas fungi have an analogous structure called the spindle pole body (Marshall 2009). The centrosome is composed by two centrioles surrounded by the pericentriolar material (PCM) (Nigg and Raff 2009) (for a discussion of PCM structure and function, see also the Chap. 3 by Comartin and Pelletier). Centrioles are cylindrical structures made of nine microtubule triplets arranged in a ninefold symmetry. They recruit and organise a large number of proteins forming the PCM (Bobinnec et al. 1998). D. Gambarotto • R. Basto (*) Subcellular Structure and Cellular Dynamics, Institut Curie PSL Research University, CNRS UMR144, 12 rue Lhomond, Paris 75005, France e-mail: [email protected] # Springer-Verlag Wien 2016 J. Lu¨ders (ed.), The Microtubule Cytoskeleton, DOI 10.1007/978-3-7091-1903-7_5
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Centriole number is tightly regulated. For most part of the cell cycle, the two centrioles are linked and placed orthogonally to each other. This configuration is called centriole engagement, and a new centriole is not formed as long as the pre-existing centrioles are engaged (Tsou and Stearns 2006). Centriole disengagement takes place usually at the end of mitosis when the daughter cells inherit one centrosome with two separated centrioles (Kuriyama and Borisy 1981). Centriole disengagement is thought to be the licence to allow centriole duplication (Tsou and Stearns 2006), which occurs only once per cell cycle. Five proteins, ZYG-1, SPD-2, SAS-4, SAS-5 and SAS-6, were identified in Caenorhabditis elegans as essential for centriole biogenesis (Dammermann et al. 2004; Delattre et al. 2004; Kemp et al. 2004; Kirkham et al. 2003; Leidel et al. 2005; Leidel and Gonczy 2003; O’Connell et al. 2001; Pelletier et al. 2004). These proteins are recruited in a precise temporal order (Delattre et al. 2006; Pelletier et al. 2006). SPD-2 is the first to be recrui
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