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

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.

VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes

“…3 At the base of each procentriole, Sas6 forms the central hub of a "cartwheel" that establishes the 9-fold symmetry of the centriole 4,5 and behaves as the scaffold onto which other centriolar proteins are assembled during centriole assembly. 3,6 During quiescence, the mother centriole is converted to a basal body to organize a primary cilium that is resorbed during cell cycle re-entry. 7 The Mps1 protein kinase is essential for the spindle assembly checkpoint 8 and modulates centriole assembly in vertebrates.…”

Characterization of novel MPS1 inhibitors with preclinical anticancer activity

“…11 In addition, MPS1 may be required for centrosome duplication. 26 Finally, MPS1 has been implicated in surveillance mechanisms such as the G 2 /M checkpoint (by interacting with checkpoint kinase 2 and Bloom syndrome) 27,28 and the tetraploidy checkpoint (by phosphorylating the oncosuppressor protein p53), 29 which prevent the initiation of mitosis in cells with damaged or unreplicated DNA 30,31 and the proliferation/survival of illicitly generated polyploids, [32][33][34] respectively.…”

Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes

“…γ-tubulin, being a major PCM component greatly accumulates at centrosomes during centrosome maturation that takes place at G2 phase 31,32 , and this increase makes it a poor internal standard for assessing cell cycle variations of other centrosomal proteins. On the other hand, Sas6 is recruited to procentrioles during early S-phase to stimulate assembly of the cartwheels 4,5,7 , and remains at the base of the newly formed centrioles until cells enter mitosis when it begins to be degraded (Figure 2 and reference 5 ). However, in HeLa or U2OS cells, the centriolar level of Sas6 gradually increases as cells progress from S-phase to G2 phase 5 .…”

“…Sas6 that is indispensable for centriole assembly is recruited to form the hub of the cartwheel [4][5][6] . Other centriolar proteins are then assembled onto the cartwheel in a highly regulated, proximal to distal manner 7 . After precisely completing centriole duplication, cells assemble additional pericentriolar materials to build two functional centrosomes by the end of G2 phase 8 .…”