Deconstructing the centriole: structure and number control

Brito, Daniela A.; Gouveia, Susana Montenegro; Bettencourt-Dias, Mónica

doi:10.1016/j.ceb.2012.01.003

Cited by 117 publications

(130 citation statements)

References 59 publications

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“…Neuroprogenitors depleted of ASPM fail to orient the mitotic spindle perpendicular to the ventricular surface of the neuroepithelium giving asymmetric, rather than symmetric, divisions (Fish et al 2006). Mutations in CPAP (MCPH6) and STIL (MCPH7) also affect spindle orientation (Kitagawa et al 2011b;Brito et al 2012). Other genes for centrosomal proteins that are mutated in microcephaly include the CNN homolog, CDK5RAP2 (MCPH3), required for centrosome maturation and DNA damage-induced G 2 arrest (Barr et al 2010;Lizarraga et al 2010), and CEP63 with its partner Cep152, which participate in centriole assembly (Sir et al 2011).…”

Section: The Centrosome and Its Duplication Cyclementioning

confidence: 99%

The Centrosome and Its Duplication Cycle

Hagan

Glover

2015

Cold Spring Harb Perspect Biol

203

193

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Section: The Centrosome and Its Duplication Cyclementioning

confidence: 99%

The Centrosome and Its Duplication Cycle

Hagan

Glover

2015

Cold Spring Harb Perspect Biol

203

193

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“…Centrioles exist as pairs and are composed of an older (mother) centriole and a younger (daughter) centriole. Centrioles duplicate once per cell cycle in a tightly controlled manner to ensure that an interphase centrosome is duplicated exactly once per cell cycle (Firat-Karalar and Stearns, 2014;Brito et al, 2012;Gonczy, 2012). Abnormalities in centriole number and structure can lead to the formation of extra centrosomes that can perturb spindle organization and chromosome segregation giving rise to aneuploidy (Gonczy, 2015).…”

Section: Introductionmentioning

confidence: 99%

Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication

Brunk

Zhu

Bärenz

et al. 2016

Journal of Cell Science

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Centrioles are core components of centrosomes, the major microtubule-organizing centers of animal cells, and act as basal bodies for cilia formation. Control of centriole number is therefore crucial for genome stability and embryogenesis. Centriole duplication requires the serine/threonine protein kinase Plk4. Here, we identify Cep78 as a human centrosomal protein and a new interaction partner of Plk4. Cep78 is mainly a centriolar protein that localizes to the centriolar wall. Furthermore, we find that Plk4 binds to Cep78 through its N-terminal domain but that Cep78 is not an in vitro Plk4 substrate. Cep78 colocalizes with Plk4 at centrioles and is required for Plk4-induced centriole overduplication. Interestingly, upon depletion of Cep78, newly synthesized Plk4 is not localized to centrosomes. Our results suggest that the interaction between Cep78 and the N-terminal catalytic domain of Plk4 is a new and important element in the centrosome overduplication process.

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“…Centrosomes are composed of two orthogonally arranged centrioles surrounded by an amorphous mass of electron-dense pericentriolar material (PCM). Centrioles duplicate precisely once per cell cycle and serve as platforms for the assembly of centrosomes, primary cilia, and flagella (1)(2)(3)(4).…”

mentioning

confidence: 99%

Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152

Kim

Park

Shukla

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

194

269

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Significance Found in most eukaryotic cells, a centriole is a cylindrically shaped subcellular structure that plays an important role in various cellular processes, including mitotic spindle formation and chromosome segregation. Centriole duplication occurs only once per cell cycle, thus ensuring accurate control of centriole numbers to maintain genomic integrity. Although a growing body of evidence suggests that a Ser/Thr protein kinase, polo-like kinase 4 (Plk4), is a key regulator of centriole duplication, how Plk4 is recruited to centrosomes remains largely unknown. Here we showed that Plk4 dynamically localizes to distinct subcentrosomal regions by interacting with two hierarchically regulated scaffolds, Cep192 and Cep152. Highlighting the importance of these interactions, mutational disruption of either one of these interactions was sufficient to cripple Plk4-dependent centriole biogenesis.

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Deconstructing the centriole: structure and number control

Cited by 117 publications

References 59 publications

The Centrosome and Its Duplication Cycle

The Centrosome and Its Duplication Cycle

Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication

Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152

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