Phosphorylation of the Yeast γ-Tubulin Tub4 Regulates Microtubule Function

Lin, Tien-chen; Gombos, Linda; Neuner, Annett; Sebastian, Dominik; Olsen, Jesper V.; Hrle, Ajla; Benda, Christian; Schiebel, Elmar

doi:10.1371/journal.pone.0019700

Cited by 44 publications

(56 citation statements)

References 71 publications

(131 reference statements)

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“…Both groups showed that phosphorylation of g-tubulin (Tub4) is functionally important, as previously shown for Y445 (Vogel et al 2001; position Y445 verified in Keck et al 2011). Lin et al (2011) found that phospho-mimetic mutations in TUB4 at S74, S100, and S360 are lethal. Keck et al (2011) showed that the highly conserved Tub4-S360 was phosphorylated in vivo and is a CDK site in vitro as predicted by its sequence.…”

Section: Regulation Of Spb Duplicationsupporting

confidence: 52%

“…Recent phospho-proteomics studies of overexpressed g-tubulin complexes (Tub4, Spc97, Spc98) (Lin et al 2011) and of entire intact SPBs (Keck et al 2011) revealed extensive phosphorylation of SPB components. For example, Keck et al (2011) report 297 phosphorylation sites over the 17 of 18 core SPB components; only Mps3 lacked mapped sites, likely due to poor coverage of this membrane protein.…”

Section: Regulation Of Spb Duplicationmentioning

confidence: 99%

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Mitotic Spindle Form and Function

2012

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The Saccharomyces cerevisiae mitotic spindle in budding yeast is exemplified by its simplicity and elegance. Microtubules are nucleated from a crystalline array of proteins organized in the nuclear envelope, known as the spindle pole body in yeast (analogous to the centrosome in larger eukaryotes). The spindle has two classes of nuclear microtubules: kinetochore microtubules and interpolar microtubules. One kinetochore microtubule attaches to a single centromere on each chromosome, while approximately four interpolar microtubules emanate from each pole and interdigitate with interpolar microtubules from the opposite spindle to provide stability to the bipolar spindle. On the cytoplasmic face, two to three microtubules extend from the spindle pole toward the cell cortex. Processes requiring microtubule function are limited to spindles in mitosis and to spindle orientation and nuclear positioning in the cytoplasm. Microtubule function is regulated in large part via products of the 6 kinesin gene family and the 1 cytoplasmic dynein gene. A single bipolar kinesin (Cin8, class Kin-5), together with a depolymerase (Kip3, class Kin-8) or minus-end-directed kinesin (Kar3, class Kin-14), can support spindle function and cell viability. The remarkable feature of yeast cells is that they can survive with microtubules and genes for just two motor proteins, thus providing an unparalleled system to dissect microtubule and motor function within the spindle machine.

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Section: Regulation Of Spb Duplicationsupporting

confidence: 52%

Section: Regulation Of Spb Duplicationmentioning

confidence: 99%

Mitotic Spindle Form and Function

2012

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“…At higher temperatures cells arrest in mitosis with short bipolar spindles containing disorganized microtubules. However, these defects seem to be caused, in part, by destabilization of c-tubulin (Lin et al, 2011). Characterization of additional phosphorylation sites, which were identified in yeast cTuSC subunits that are bound to spindle pole bodies (Keck et al, 2011;Lin et al, 2011) and present in the cytoplasm (Lin et al, 2011), might provide further insight into the regulation of c-tubulin complexes.…”

Section: Phosphorylation Of C-tubulin and Grip-gcpsmentioning

confidence: 99%

The where, when and how of microtubule nucleation – one ring to rule them all

Teixidó-Travesa¹,

Roig

Lüders³

2012

Journal of Cell Science

154

162

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SummaryThe function of microtubules depends on their arrangement into highly ordered arrays. Spatio-temporal control over the formation of new microtubules and regulation of their properties are central to the organization of these arrays. The nucleation of new microtubules requires c-tubulin, an essential protein that assembles into multi-subunit complexes and is found in all eukaryotic organisms. However, the way in which c-tubulin complexes are regulated and how this affects nucleation and, potentially, microtubule behavior, is poorly understood. c-tubulin has been found in complexes of various sizes but several lines of evidence suggest that only large, ring-shaped complexes function as efficient microtubule nucleators. Human c-tubulin ring complexes (cTuRCs) are composed of c-tubulin and the c-tubulin complex components (GCPs) 2, 3, 4, 5 and 6, which are members of a conserved protein family. Recent work has identified additional unrelated cTuRC subunits, as well as a large number of more transient cTuRC interactors. In this Commentary, we discuss the regulation of cTuRC-dependent microtubule nucleation as a key mechanism of microtubule organization. Specifically, we focus on the regulatory roles of the cTuRC subunits and interactors and present an overview of other mechanisms that regulate cTuRC-dependent microtubule nucleation and organization.

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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). Phosphorylation of the adapter in the region between the two motifs further enhances the interaction.…”

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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Phosphorylation of the Yeast γ-Tubulin Tub4 Regulates Microtubule Function

Cited by 44 publications

References 71 publications

Mitotic Spindle Form and Function

Mitotic Spindle Form and Function

The where, when and how of microtubule nucleation – one ring to rule them all

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

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