Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function

Sawant, Dwitiya; Majumder, Shubhra; Perkins, Jennifer; Yang, Chang‐Hsien; Eyers, Patrick A.; Fisk, Harold A.

doi:10.1091/mbc.e14-07-1248

Cited by 19 publications

(12 citation statements)

References 58 publications

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“…Given that the Ca 2+ binding proteins calmodulin (22) and centrin-2 (49) are required for mitosis, this work now provides the missing link that connects the cell biology of Ca 2+ signaling with mitosis in mammalian cells and has important implications for furthering our understanding of normal growth, development, and ageing. Because centrins-2 and -3 are centrosome-associated Ca 2+ binding proteins (50), this could be a clue as to why a centrosome-localized Ca 2+ signal is of crucial importance. Centrosomally localized Ca 2+ signaling is likely a universal phenomenon essential during mitosis and represents an entirely novel control mechanism that opens new avenues of investigation into modulating cell division.…”

Section: Discussionmentioning

confidence: 99%

A centrosome‐localized calcium signal is essential for mammalian cell mitosis

et al. 2019

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Mitosis defects can lead to premature ageing and cancer. Understanding mitosis regulation therefore has important implications for human disease. Early data suggested that calcium (Ca2+) signals could influence mitosis, but these have hitherto not been observed in mammalian cells. Here, we reveal a prolonged yet spatially restricted Ca2+ signal at the centrosomes of actively dividing cells. Local buffering of the centrosomal Ca2+ signals, by flash photolysis of the caged Ca2+ chelator diazo-2-acetoxymethyl ester, arrests mitosis. We also provide evidence that this Ca2+ signal emanates from the endoplasmic reticulum. In summary, we characterize a unique centrosomal Ca2+ signal as a functionally essential input into mitosis.—Helassa, N., Nugues, C., Rajamanoharan, D., Burgoyne, R. D., Haynes, L. P. A centrosome-localized calcium signal is essential for mammalian cell mitosis.

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Section: Discussionmentioning

confidence: 99%

A centrosome‐localized calcium signal is essential for mammalian cell mitosis

et al. 2019

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“…This could be because Sfr1 acts independently of centrin or because this role for centrin may have been undetectable in previous studies of centrin-null cells that display the full effects of centrin loss (21, 30, 31). Intriguingly, it has recently been shown that human Cetn3 can antagonize human Cetn2 function in centriole assembly, highlighting a role for Cetn3 in the inhibition of centrosome duplication (60). Depletion of Cetn3 in HeLa cells resulted in the overproduction of centrioles, providing an exciting potential parallel to our observed overproduction of basal bodies upon loss of the centrin-binding protein Sfr1.…”

Section: Discussionmentioning

confidence: 99%

Sfr1, a Tetrahymena thermophila Sfi1 Repeat Protein, Modulates the Production of Cortical Row Basal Bodies

Heydeck

Stemm-Wolf

Knop

et al. 2016

mSphere

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Basal bodies and centrioles are structurally similar and, when rendered dysfunctional as a result of improper assembly or maintenance, are associated with human diseases. Centrins are conserved and abundant components of both structures whose basal body and centriolar functions remain incompletely understood. Despite the extensive study of centrins in Tetrahymena thermophila, little is known about how centrin-binding proteins contribute to centrin’s roles in basal body assembly, stability, and orientation. The sole previous study of the large centrin-binding protein family in Tetrahymena revealed a role for Sfr13 in the stabilization and separation of basal bodies. In this study, we found that Sfr1 localizes to all Tetrahymena basal bodies and complete genetic deletion of SFR1 leads to overproduction of basal bodies. The uncovered inhibitory role of Sfr1 in basal body production suggests that centrin-binding proteins, as well as centrins, may influence basal body number both positively and negatively.

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“…Further, there was marked variability in the percentage of cells with supernumerary centrioles, indicating that cancer cell lines possess distinct centriole numbers and levels of centrosome amplification. Interestingly, hPOC5 is capable of binding both human CETN2 and human CETN3, which have roles in promoting and antagonizing centrosome duplication, respectively (Sawant et al, 2015). Thus, depletion of CETN3 in HeLa cells results in a centriole overproduction, suggesting that centrins are important for modulating centriole number and this bidirectional contribution to centrosome duplication may be impaired in some human cancers.…”

Section: Discussionmentioning

confidence: 99%

TetrahymenaPoc5 is a transient basal body component that is important for basal body maturation

Heydeck

Bayless²,

Stemm-Wolf

et al. 2019

Preprint

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ABSTRACTBasal bodies (BBs) are microtubule-based organelles that template and stabilize cilia at the cell surface. Centrins ubiquitously associate with BBs and function in BB assembly, maturation, and stability. Human POC5 (hPOC5) is a highly conserved centrin-binding protein that binds centrins through Sfi1p-like repeats and is required for building full-length, mature centrioles. Here, we use the BB-rich cytoskeleton of Tetrahymena thermophila to characterize Poc5 BB functions. Tetrahymena Poc5 (TtPoc5) uniquely incorporates into assembling BBs and is then removed from mature BBs prior to ciliogenesis. Complete genomic knockout of TtPOC5 leads to a significantly increased production of BBs yet a markedly reduced ciliary density, both of which are rescued by reintroduction of TtPoc5. A second Tetrahymena POC5-like gene, SFR1, is similarly implicated in modulating BB production. When TtPOC5 and SFR1 are co-deleted, cell viability is compromised, and levels of BB overproduction are exacerbated. Overproduced BBs display defective transition zone formation and a diminished capacity for ciliogenesis. This study uncovers a requirement for Poc5 in building mature BBs, providing a possible functional link between hPOC5 mutations and impaired cilia.SUMMARY STATEMENTLoss of Tetrahymena thermophila Poc5 reveals an important role for this centrin-binding protein in basal body maturation, which also impacts basal body production and ciliogenesis.

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Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function

Cited by 19 publications

References 58 publications

A centrosome‐localized calcium signal is essential for mammalian cell mitosis

A centrosome‐localized calcium signal is essential for mammalian cell mitosis

Sfr1, a Tetrahymena thermophila Sfi1 Repeat Protein, Modulates the Production of Cortical Row Basal Bodies

TetrahymenaPoc5 is a transient basal body component that is important for basal body maturation

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