Roles of β-Tubulin Residues Ala428 and Thr429 in Microtubule Formation in Vivo

Joe, Patrick A.; Banerjee, Amitav; Ludueña, Richard F.

doi:10.1074/jbc.m807491200

Cited by 25 publications

(19 citation statements)

References 75 publications

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“…The C Terminus of ␣-Tubulin Is Necessary for Microtubule Incorporation-It was recently shown that the deletion of the charged C-terminal tail of ␤-tubulin impedes its incorporation in the microtubule network in vivo (42). The present results show that this is also the case with ␣-tubulin truncated of its 23 last residues (GFP-Tub⌬23C).…”

Section: Discussionsupporting

confidence: 67%

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

Lefèvre¹,

Chernov

Joshi

et al. 2011

Journal of Biological Chemistry

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The C-terminal region of tubulin is involved in multiple aspects of the regulation of microtubule assembly. To elucidate the molecular mechanisms of this regulation, we study here, using different approaches, the interaction of Tau Microtubules are involved in a number of critical cellular processes, such as the determination of cell shape, chromosome segregation, intracellular transport of vesicles and organelles, and cell migration. Microtubules consist mainly of ␣␤-tubulin heterodimers organized head-to-tail into protofilaments whose parallel self-association gives rise to microtubules (1-4). ␣-and ␤-tubulin monomers have each a molecular mass of 50 kDa and are organized in three domains, namely the N-terminal domain (amino acid residues 1-205) involved in nucleotide binding, the intermediate domain (amino acid residues 206 -384), and the C-terminal domain (amino acid residue 385 to the C terminus) (5). The C-terminal domain of tubulin represents a critical part of the binding site of different tubulin/microtubules partners, such as MAPs, 4 which are major regulators of microtubule dynamics (6 -8), or polycations, which promote tubulin assembly in vitro in different polymeric forms (9). The C-terminal domain comprises a highly negatively charged tail of about 20 amino acid residues (named herein the C-terminal tail (CTT)), which protrudes from the surface of microtubules. In agreement with its participation in the regulation of microtubule assembly through interactions with partners, the CTT is also the most divergent part of tubulin, and variations among tubulin isotypes (10) may explain the modulation of the dynamics of microtubule assembly in specific tissues or cytoplasmic regions.Different structure information has been obtained regarding the C-terminal domain of tubulin by using either fulllength tubulin or peptide fragments. Electron crystallography of zinc-induced tubulin sheets showed the presence of two anti-parallel ␣-helices (helix H11 (amino acid residues 385-397) and helix H12 (amino acid residues 418 -433)) lying at the outer surface of tubulin. The regions corresponding to the CTTs of either ␣-or ␤-tubulin were however not observed, probably due to the flexibility of this part of the protein (5). These observations were confirmed by x-ray diffraction analyses of crystal complexes formed between tubulin and the RB3-stathmin-like domain (11-13). Other structural data were obtained with peptides from the C-terminal region of tubulin studied either when free in solution or in interaction with different partners. NMR structure investigations on ␣-and ␤-tubulin C-terminal peptides showed that both ␣ (residues 404 -451) and ␤ (residues 394 -445) peptides have no defined secondary structure in aqueous solution but contain a well □ S The on-line version of this article (available at http://www.jbc.org) contains supplemental 4 The abbreviations used are: MAP, microtubule-associated protein; ␣Tub410C, amino acid residues 410 -451 from ␣1a-tubulin; CTT, tubulin C-terminal tail; ITC, isothermal titration ...

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Section: Discussionsupporting

confidence: 67%

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

Lefèvre¹,

Chernov

Joshi

et al. 2011

Journal of Biological Chemistry

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“…Bands were transferred to nitrocellulose membranes and treated with isotype-specific monoclonal antibodies followed by horseradish peroxidase as described by Joe et al (2009). Bands were quantitated by image analysis using the Odyssey software (LI-COR Biosciences).…”

Section: Methodsmentioning

confidence: 99%

The β isotypes of tubulin in neuronal differentiation

2010

Self Cite

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The differences among the vertebrate β isotypes of tubulin are highly conserved in evolution, suggesting that they have functional significance. To address this, we have used differentiating neuroblastoma cells as a model system. These cells express the βI, βII, and βIII isotypes. Although there is no difference prior to differentiation, a striking difference is seen after differentiation. Both βI and βIII occur in cell bodies and neurites, while βII occurs mostly in neurites. Knocking down βI causes a large decrease in cell viability while silencing βII and βIII does not. Knocking down βII causes a large decrease in neurite outgrowth without affecting viability. Knocking down βIII has little effect on neurite outgrowth and only decreases viability if cells are treated with glutamate and glycine, a combination known to generate free radicals and reactive oxygen species. It appears, therefore, that βI is required for cell viability, βII for neurite outgrowth and βIII for protection against free radicals and reactive oxygen species.

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“…Unlike the bII-and bIV-tubulin isotypes bIII-tubulin is phosphorylated at a serine in the C-terminus (Khan and Ludueña, 1996;Ludueña and Banerjee, 2008b). Also, unlike in other b-tubulin isotypes, in the bIII isotype, the presence of threonine residue Thr(429) strongly favors microtubule assembly (Joe et al, 2009). And finally, notwithstanding its restricted and highly selective (predominantly neuronal) cell type distribution in normal organs and tissues, the bIII isotype is widely, albeit differentially, expressed in a broad range of human tumors of neuronal and non-neuronal origin (Katsetos et al, 2003a,b).…”

Section: Microtubules and Tubulinsmentioning

confidence: 97%

Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. class III β‐tubulin

Katsetos

Dráberová

Legido

et al. 2009

Journal Cellular Physiology

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Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain cancer in adults. Despite advances in molecular biology and genetics of gliomas currently there is no effective treatment or promising molecularly targeted experimental therapeutic strategies for these tumors. In previous studies we have shown aberrant overexpression of the class III beta-tubulin isotype (betaIII-tubulin) in GBM and have proposed that this change may reflect perturbations in microtubule dynamics associated with glioma tumorigenesis, tumor progression and malignant transformation into GBM. This minireview focuses on microtubules and tubulin as emerging targets in potential therapy of GBM using a new class of betaIII-tubulin-targeted drugs in the light of recent developments concerning the function and potential role of this isotype in clinically aggressive tumor behavior, cancer stem cells, tumor hypoxia and chemoresistance to tubulin binding agents, principally taxanes.

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Roles of β-Tubulin Residues Ala428 and Thr429 in Microtubule Formation in Vivo

Cited by 25 publications

References 75 publications

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

The β isotypes of tubulin in neuronal differentiation

Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. class III β‐tubulin

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