Centriole assembly and the role of Mps1: defensible or dispensable?

In proliferating cells, organization of a bipolar mitotic spindle is facilitated by the presence of two mature centrosomes, each of which contains a pair of centrioles. Accordingly, the single centrosome that proliferating cells inherit must be precisely duplicated exactly once prior to mitosis [1]. The proper structure and function of centrosomes is dependent upon the strict doubling of existing centrioles [2], making the molecular mechanisms underlying the centriole assembly cycle of particular importance in the maintenance of genomic integrity.The canonical centrosome assembly pathway results in the construction of a single procentriole at a site adjacent to each existing centriole (Figure 1). Much of what is known about centrosome duplication is derived from studies in model organisms [3,4]. A powerful proteomic and comparative genomic analysis in green algae led to the characterization of 18 core proteins that form the Proteome of Centrioles, called the Poc proteins [5], and genome-wide RNAi screens in C. elegans identified five essential centriole biogenesis proteins, SPD-2, ZYG-1, SAS-4, SAS-5, and SAS-6 [6,7]. Live cell imaging of worm embryos placed these proteins into an ordered assembly pathway: pro-centriole formation is initiated by the recruitment of SPD-2 to an existing centriole, SPD-2 leads to recruitment of the ZYG-1 protein kinase, which in turn recruits a complex containing SAS-5 and SAS-6 that promotes the formation of a central tube that determines basic centriole structure, followed by SAS-4 that facilitates the assembly of microtubules and mediates pro-centriole elongation [6-11]. The procentriole formation pathway delineated in C. elegans represents a core centriole assembly program that is conserved in organisms as distinct as T. thermophila [12], D. melanogaster [13] and H. sapiens [14-16]. The past year has seen an explosion in our understanding of the canonical centriole assembly pathway in humans. The human SPD-2 orthologue Cep192 is re