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

Pike AN, Fisk HA - Cell Div (2011)

Bottom Line: The Mps1 protein kinase is an intriguing and controversial player in centriole assembly.Recent studies of Mps1 have identified at least two distinct functions for Mps1 in centriole assembly, while simultaneously supporting the notion that Mps1 is dispensable for the process.However, the fact that at least one centrosomal substrate of Mps1 is conserved from yeast to humans down to the phosphorylation site, combined with evidence demonstrating the exquisite control exerted over centrosomal Mps1 levels suggest that the notion of being essential may not be the most important of distinctions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Genetics, The Ohio State University, 484 W, 12th Avenue, Columbus OH 43210-1292, USA. fisk.13@osu.edu.

ABSTRACT
The Mps1 protein kinase is an intriguing and controversial player in centriole assembly. Originally shown to control duplication of the budding yeast spindle pole body, Mps1 is present in eukaryotes from yeast to humans, the nematode C. elegans being a notable exception, and has also been shown to regulate the spindle checkpoint and an increasing number of cellular functions relating to genomic stability. While its function in the spindle checkpoint appears to be both universally conserved and essential in most organisms, conservation of its originally described function in spindle pole duplication has proven controversial, and it is less clear whether Mps1 is essential for centrosome duplication outside of budding yeast. Recent studies of Mps1 have identified at least two distinct functions for Mps1 in centriole assembly, while simultaneously supporting the notion that Mps1 is dispensable for the process. However, the fact that at least one centrosomal substrate of Mps1 is conserved from yeast to humans down to the phosphorylation site, combined with evidence demonstrating the exquisite control exerted over centrosomal Mps1 levels suggest that the notion of being essential may not be the most important of distinctions.

No MeSH data available.


Centriole assembly as a modular process. Centriole assembly in human cells proceeds through a pathway analogous to that described in C. elegans, but requires several additional proteins not present in worms, and proceeds through a cartwheel template as opposed to a central tube. Centrioles are not templates per se, but rather provide a surface for the assembly of cartwheels, depicted as a hub composed of hSas6 (red) and 9 symmetrical spokes (blue). We propose that cartwheels then serve as a platform onto which additional centriole modules are assembled in a proximal to distal, or "bottom-up" fashion. Yellow and green rectangles are used to depict proximal (yellow) and distal (green) centriole modules. The frame surrounding these modules is meant to depict maturation into the final structure rather than centriolar microtubules.
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Figure 1: Centriole assembly as a modular process. Centriole assembly in human cells proceeds through a pathway analogous to that described in C. elegans, but requires several additional proteins not present in worms, and proceeds through a cartwheel template as opposed to a central tube. Centrioles are not templates per se, but rather provide a surface for the assembly of cartwheels, depicted as a hub composed of hSas6 (red) and 9 symmetrical spokes (blue). We propose that cartwheels then serve as a platform onto which additional centriole modules are assembled in a proximal to distal, or "bottom-up" fashion. Yellow and green rectangles are used to depict proximal (yellow) and distal (green) centriole modules. The frame surrounding these modules is meant to depict maturation into the final structure rather than centriolar microtubules.

Mentions: 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 required for both centriole biogenesis and centrosome maturation, binds to Plk4, and is required for Plk4-dependent centriole overproduction [17], suggesting that it might function analogously to SPD-2. However, Plk4 recruitment also requires Cep152, the human orthologue of D. melanogaster asterless [18,19]. Recruitment of Plk4, the distant relative and presumptive functional counterpart to ZYG-1 [15,16,20], is then followed by that of hSas6 [14,15] and the human orthologue of Sas-4, CPAP/CENP-J [21-23]. Several additional proteins are recruited during S and G2 to promote procentriole assembly and elongation, including Cep135 [15,24], γ-tubulin, and CP110 [15,25]. However, centriole assembly in human cells involves many additional proteins not found in worms, including δ- and ε- tubulins [26,27], Mps1 [28-32], Centrin 2 (Cetn2) [28,33], hPoc5 [34], and Cep76 [35], among others.


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

Pike AN, Fisk HA - Cell Div (2011)

Centriole assembly as a modular process. Centriole assembly in human cells proceeds through a pathway analogous to that described in C. elegans, but requires several additional proteins not present in worms, and proceeds through a cartwheel template as opposed to a central tube. Centrioles are not templates per se, but rather provide a surface for the assembly of cartwheels, depicted as a hub composed of hSas6 (red) and 9 symmetrical spokes (blue). We propose that cartwheels then serve as a platform onto which additional centriole modules are assembled in a proximal to distal, or "bottom-up" fashion. Yellow and green rectangles are used to depict proximal (yellow) and distal (green) centriole modules. The frame surrounding these modules is meant to depict maturation into the final structure rather than centriolar microtubules.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094359&req=5

Figure 1: Centriole assembly as a modular process. Centriole assembly in human cells proceeds through a pathway analogous to that described in C. elegans, but requires several additional proteins not present in worms, and proceeds through a cartwheel template as opposed to a central tube. Centrioles are not templates per se, but rather provide a surface for the assembly of cartwheels, depicted as a hub composed of hSas6 (red) and 9 symmetrical spokes (blue). We propose that cartwheels then serve as a platform onto which additional centriole modules are assembled in a proximal to distal, or "bottom-up" fashion. Yellow and green rectangles are used to depict proximal (yellow) and distal (green) centriole modules. The frame surrounding these modules is meant to depict maturation into the final structure rather than centriolar microtubules.
Mentions: 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 required for both centriole biogenesis and centrosome maturation, binds to Plk4, and is required for Plk4-dependent centriole overproduction [17], suggesting that it might function analogously to SPD-2. However, Plk4 recruitment also requires Cep152, the human orthologue of D. melanogaster asterless [18,19]. Recruitment of Plk4, the distant relative and presumptive functional counterpart to ZYG-1 [15,16,20], is then followed by that of hSas6 [14,15] and the human orthologue of Sas-4, CPAP/CENP-J [21-23]. Several additional proteins are recruited during S and G2 to promote procentriole assembly and elongation, including Cep135 [15,24], γ-tubulin, and CP110 [15,25]. However, centriole assembly in human cells involves many additional proteins not found in worms, including δ- and ε- tubulins [26,27], Mps1 [28-32], Centrin 2 (Cetn2) [28,33], hPoc5 [34], and Cep76 [35], among others.

Bottom Line: The Mps1 protein kinase is an intriguing and controversial player in centriole assembly.Recent studies of Mps1 have identified at least two distinct functions for Mps1 in centriole assembly, while simultaneously supporting the notion that Mps1 is dispensable for the process.However, the fact that at least one centrosomal substrate of Mps1 is conserved from yeast to humans down to the phosphorylation site, combined with evidence demonstrating the exquisite control exerted over centrosomal Mps1 levels suggest that the notion of being essential may not be the most important of distinctions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Genetics, The Ohio State University, 484 W, 12th Avenue, Columbus OH 43210-1292, USA. fisk.13@osu.edu.

ABSTRACT
The Mps1 protein kinase is an intriguing and controversial player in centriole assembly. Originally shown to control duplication of the budding yeast spindle pole body, Mps1 is present in eukaryotes from yeast to humans, the nematode C. elegans being a notable exception, and has also been shown to regulate the spindle checkpoint and an increasing number of cellular functions relating to genomic stability. While its function in the spindle checkpoint appears to be both universally conserved and essential in most organisms, conservation of its originally described function in spindle pole duplication has proven controversial, and it is less clear whether Mps1 is essential for centrosome duplication outside of budding yeast. Recent studies of Mps1 have identified at least two distinct functions for Mps1 in centriole assembly, while simultaneously supporting the notion that Mps1 is dispensable for the process. However, the fact that at least one centrosomal substrate of Mps1 is conserved from yeast to humans down to the phosphorylation site, combined with evidence demonstrating the exquisite control exerted over centrosomal Mps1 levels suggest that the notion of being essential may not be the most important of distinctions.

No MeSH data available.