Targeting of γ-tubulin complexes to microtubule organizing centers: conservation and divergence

Lin, Tien-chen; Neuner, Annett; Schiebel, Elmar

doi:10.1016/j.tcb.2014.12.002

Cited by 120 publications

(129 citation statements)

References 134 publications

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“…Finally, three proteins associated with the γ‐TuRC, Nedd1 (Haren et al , 2006; Luders et al , 2006) and Mozart 1, and Mozart 2 (Hutchins et al , 2010; Teixido‐Travesa et al , 2010) are similarly abundant as the GCP2 and GCP3 core components of γ‐TuSC. These data extend previous biochemical studies (Murphy et al , 2001; Choi et al , 2010) and support the notion that multiple γ‐TuSCs associate with GCP4, GCP5, and GCP6 into γ‐TuRCs (Kollman et al , 2011; Lin et al , 2015). …”

Section: Resultssupporting

confidence: 90%

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: Resultssupporting

confidence: 90%

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

et al. 2016

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“…Here, interactions with adapter proteins containing CM1 and SPM motifs might trigger formation of γTuSC oligomers that are similar in structure and activity to γTuRC (Kollman et al, 2010;Lin et al, 2015Lin et al, , 2014. The CM1 and SPM motifs of the budding yeast adapter Spc110 have been shown to mediate interaction with γTuSC, through direct interaction with the Nterminus of GCP3 and possibly also GCP2 (Knop and Schiebel, 1997;Lin et al, 2011;Nguyen et al, 1998).…”

Section: Introductionmentioning

confidence: 98%

“…Thus, the activity of γTuRC is tightly controlled by targeting and activation factors that spatially restrict nucleation to microtubule-organizing centers (MTOCs) such as the centrosome. Surprisingly, whereas assembly and targeting of human γTuRC seem to involve all GCPs (Bahtz et al, 2012;Choi et al, 2010;Izumi et al, 2008;Scheidecker et al, 2015), only γ-tubulin, GCP2 and GCP3, which form the smaller subcomplex γTuSC, are essential in flies and fungi, and are sufficient for microtubule nucleation and targeting to MTOCs (Anders et al, 2006;Fujita et al, 2002;Lin et al, 2015;Venkatram et al, 2004;Vérollet et al, 2006;Xiong and Oakley, 2009). These observations suggest that there are important organism-specific differences in the manner by which nucleation template assembly is linked to targeting and activation.…”

Section: Introductionmentioning

confidence: 99%

MZT1 regulates microtubule nucleation by linking γTuRC assembly to adapter-mediated targeting and activation

Cota

Teixidó-Travesa

Ezquerra

et al. 2017

Journal of Cell Science

135

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Regulation of the γ-tubulin ring complex (γTuRC) through targeting and activation restricts nucleation of microtubules to microtubuleorganizing centers (MTOCs), aiding in the assembly of ordered microtubule arrays. However, the mechanistic basis of this important regulation remains poorly understood. Here, we show that, in human cells, γTuRC integrity, determined by the presence of γ-tubulin complex proteins (GCPs; also known as TUBGCPs) 2-6, is a prerequisite for interaction with the targeting factor NEDD1, impacting on essentially all γ-tubulin-dependent functions. Recognition of γTuRC integrity is mediated by MZT1, which binds not only to the GCP3 subunit as previously shown, but cooperatively also to other GCPs through a conserved hydrophobic motif present in the N-termini of GCP2, GCP3, GCP5 and GCP6. MZT1 knockdown causes severe cellular defects under conditions that leave γTuRC intact, suggesting that the essential function of MZT1 is not in γTuRC assembly. Instead, MZT1 specifically binds fully assembled γTuRC to enable interaction with NEDD1 for targeting, and with the CM1 domain of CDK5RAP2 for stimulating nucleation activity. Thus, MZT1 is a 'priming factor' for γTuRC that allows spatial regulation of nucleation.

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“…The ϒ-Tubulin Ring Complex (ϒTu-RC) and the ϒ-Tubulin Small Complex (ϒTu-SC) [7,[35][36][37][38][39][40][41][42][43]. Figure 4 provides a simplified representation of this process.…”

Section: Centriolesmentioning

confidence: 99%

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2017

NTMB

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Abstract"Theranostics" refers to therapy and diagnosis. This paper presents a new method for therapy or diagnosis (or both) for malignant tumors. The underlying premise is that cancer cells with their supernumerary centrioles have a significantly higher electromagnetic field than that of normal cells. This enhanced field can then serves as a "biomarker" or target for the attraction of nanoparticles -specifically: Super Paramagnetic Nanoparticles (SPIONS) which can provide the desired theranostics. Divided into nine sections, the paper provides the bases for these assertions.

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Targeting of γ-tubulin complexes to microtubule organizing centers: conservation and divergence

Cited by 120 publications

References 134 publications

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

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

MZT1 regulates microtubule nucleation by linking γTuRC assembly to adapter-mediated targeting and activation

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