Cartwheel assembly

Hirono, Masafumi

doi:10.1098/rstb.2013.0458

Cited by 65 publications

(78 citation statements)

References 86 publications

(205 reference statements)

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“…Centrioles are microtubule‐based cylindrical structures that display evolutionarily conserved ninefold symmetry (Azimzadeh & Marshall, 2010; Hirono, 2014; Winey & O'Toole, 2014). Centrosomes are important for organelle positioning, cell shape, polarity, and motility, as well as chromosome segregation and cell division (Nigg & Stearns, 2011; Bornens, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Sas‐6 is a major component of the cartwheel and contributes to confer ninefold symmetry (van Breugel et al , 2011; Kitagawa et al , 2011; Guichard et al , 2013; Fong et al , 2014; Wang et al , 2015). The protein CPAP gets recruited to promote the assembly of microtubules onto the cartwheel (Tang et al , 2011a; Cottee et al , 2013; Sharma et al , 2016), and this step is likely assisted by Cep135 (the human homolog of Chlamydomonas Bld10) (Hirono, 2014). CPAP also cooperates with additional proteins, including CP110, in determining the length of nascent centrioles (Kohlmaier et al , 2009; Schmidt et al , 2009; Tang et al , 2009; Comartin et al , 2013; Lin et al , 2013; Sharma et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

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Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

et al. 2016

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Centrioles are essential for the formation of centrosomes and cilia. While numerical and/or structural centrosomes aberrations are implicated in cancer, mutations in centriolar and centrosomal proteins are genetically linked to ciliopathies, microcephaly, and dwarfism. The evolutionarily conserved mechanisms underlying centrosome biogenesis are centered on a set of key proteins, including Plk4, Sas‐6, and STIL, whose exact levels are critical to ensure accurate reproduction of centrioles during cell cycle progression. However, neither the intracellular levels of centrosomal proteins nor their stoichiometry within centrosomes is presently known. Here, we have used two complementary approaches, targeted proteomics and EGFP‐tagging of centrosomal proteins at endogenous loci, to measure protein abundance in cultured human cells and purified centrosomes. Our results provide a first assessment of the absolute and relative amounts of major components of the human centrosome. Specifically, they predict that human centriolar cartwheels comprise up to 16 stacked hubs and 1 molecule of STIL for every dimer of Sas‐6. This type of quantitative information will help guide future studies of the molecular basis of centrosome assembly and function.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

et al. 2016

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“…This bit of evolutionary protein engineering elegantly organizes the nine triplet microtubules of the scaffold. The assembly of the cartwheel is the focus of another section in this text [51].…”

Section: The Centriole Lumenmentioning

confidence: 99%

Centriole structure

Winey

O’Toole

2014

Phil. Trans. R. Soc. B

114

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Centrioles are among the largest protein-based structures found in most cell types, measuring approximately 250 nm in diameter and approximately 500 nm long in vertebrate cells. Here, we briefly review ultrastructural observations about centrioles and associated structures. At the core of most centrioles is a microtubule scaffold formed from a radial array of nine triplet microtubules. Beyond the microtubule triplets of the centriole, we discuss the critically important cartwheel structure and the more enigmatic luminal density, both found on the inside of the centriole. Finally, we discuss the connectors between centrioles, and the distal and subdistal appendages outside of the microtubule scaffold that reflect centriole age and impart special functions to the centriole. Most of the work we review has been done with electron microscopy or electron tomography of resin-embedded samples, but we also highlight recent work performed with cryoelectron microscopy, cryotomography and subvolume averaging. Significant opportunities remain in the description of centriolar structure, both in mapping of component proteins within the structure and in determining the effect of mutations on components that contribute to the structure and function of the centriole.

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“…A central question in the field has been to unravel the mechanisms governing the near universal ninefold symmetry of this intricate biological edifice. The discovery that proteins of the SAS-6 family can self-assemble into ring-like structures from which emanate nine spokes that resemble a slice of the cartwheel provides an organizing principle at the root of such symmetry [24,25] (figure 1b; see article by Masafumi Hirono [26]). Because the nine spokes in these structures correspond to the coiled-coil domain of SAS-6 proteins, this model suggests that the length of this domain may determine the diameter of the centriole, although whether this is the case remains to be tested.…”

Section: On Centriole Architecturementioning

confidence: 99%