Glutamylation of centriole and cytoplasmic tubulin in proliferating non-neuronal cells

Bobinnec, Yves; Moudjou, Mohammed; Fouquet, J; Desbruyères, E.; Eddé, Bernard; Bornens, Michel

doi:10.1002/(sici)1097-0169(1998)39:3<223::aid-cm5>3.0.co;2-5

Cited by 143 publications

(68 citation statements)

References 44 publications

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“…Post-translational modifications of tubulin have been shown to regulate its association with microtubule-associated proteins (43). Polyglutamylated tubulin was detected in proliferating cells of different origins (HeLa, KE37, and NIH 3T3), where it associates with the centrioles, the spindle, and the midbody (44). The localization of 4.1R coincides with that of tubulin during mitosis; thus, it is possible that the post-translational modification of tubulin in mitotic cells might facilitate their selective recruitment of 4.1R isoforms through their MBD as well as their CTD into distinct microtubule populations, hence modulating their functional properties.…”

Section: Discussionmentioning

confidence: 99%

Protein 4.1R, a Microtubule-associated Protein Involved in Microtubule Aster Assembly in Mammalian Mitotic Extract

Huang

Jagadeeswaran

Liu

et al. 2004

Journal of Biological Chemistry

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Non-erythroid protein 4.1R (4.1R) consists of a complex family of isoforms. We have shown that 4.1R isoforms localize at the mitotic spindle/spindle poles and associate in a complex with the mitotic-spindle organization proteins Nuclear Mitotic Apparatus protein (NuMA), dynein, and dynactin. We addressed the mitotic function of 4.1R by investigating its association with microtubules, the main component of the mitotic spindles, and its role in mitotic aster assembly in vitro. 4.1R appears to partially co-localize with microtubules throughout the mitotic stages of the cell cycle. In vitro sedimentation assays showed that 4.1R isoforms directly interact with microtubules. Glutathione S-transferase (GST) pull-down assays using GST-4.1R fusions and mitotic cell extracts further showed that the association of 4.1R with tubulin results from both the membrane-binding domain and C-terminal domain of 4.1R. Moreover, 4.1R, but not actin, is a mitotic microtubuleassociated protein; 4.1R associates with microtubules in the microtubule pellet of the mitotic asters assembled in mammalian cell-free mitotic extract. The organization of microtubules into asters depends on 4.1R in that immunodepletion of 4.1R from the extract resulted in randomly dispersed microtubules. Furthermore, adding a 135-kDa recombinant 4.1R reconstituted the mitotic asters. Finally, we demonstrated that a mitotic 4.1R isoform appears to form a complex in vivo with tubulin and NuMA in highly synchronized mitotic HeLa extracts. Our results suggest that a 135-kDa non-erythroid 4.1R is important to cell division, because it participates in the formation of mitotic spindles and spindle poles through its interaction with mitotic microtubules.

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Section: Discussionmentioning

confidence: 99%

Protein 4.1R, a Microtubule-associated Protein Involved in Microtubule Aster Assembly in Mammalian Mitotic Extract

Huang

Jagadeeswaran

Liu

et al. 2004

Journal of Biological Chemistry

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“…Several PTMs are present on spindle and midbody microtubules but are absent from astral microtubules. [25][26][27] Thus, tubulin PTMs may play a role in directing mitotic events including targeting of effector proteins to a subset of microtubules (for examples, see Refs. [124][125][126][127][128].…”

Section: Who Are the Interpreters Of The Tubulin Code?mentioning

confidence: 99%

“…For example, microtubules oriented towards a wound in a confluent monolayer of cells are enriched in detyrosination and acetylation 23,24 and central spindle but not astral microtubules are marked by detyrosination, glutamylation and acetylation. [25][26][27] A second parallel between chromatin and microtubules is that most PTMs take place on the tail domains of histones and tubulins that comprise the outward face of the polymer (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…[44][45][46] In mammals, tubulin glycylation is mostly restricted to axonemes of motile cilia and flagella [47][48][49] whereas glutamylation is abundant in neurons, on centrioles, in axonemes, and in spindle microtubules. 27,50,51 In ciliated protists, both polymodifications are found in numerous microtubular networks, including cytoplasmic and axonemal microtubules. 47,52,53 A major breakthrough in the identification of PTM enzymes was achieved recently with the identification of a gene family that carries out tubulin glutamylation.…”

Section: Introductionmentioning

confidence: 99%

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The Tubulin Code

Verhey

Gaertig²

2007

Cell Cycle

491

393

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AbbreViAtions PTMposttranslational modification CTT C-terminal tail TTL tubulin tyrosine ligase TTLL TTL-like enzyme MAP microtubule associated protein +TIP plus-end tracking protein CLIP cytoplasmic linker protein AcKnowledGementsWe thank Marie-Helene Bré, David Allis, and Ray Trievel for stimulating discussions and reading the manuscript. Work in our labs is supported by the NSF (033965 to J.G.) and NIH (GM070862 to K.J.V.). AbstrActMicrotubules create diverse arrays with specific cellular functions such as the mitotic spindle, cilia and bundles inside neurons. How microtubules are regulated to enable specific functions is not well understood. Recent work has shown that posttranslational modifications of the tubulin building blocks mark subpopulations of microtubules and selectively affect downstream microtubule-based functions. In this way, the tubulin modifications generate a "code" that can be read by microtubule-associated proteins in a manner analogous to how the histone code directs diverse chromatin functions. Here we review recent progress in understanding how the tubulin code is generated, maintained, and read by microtubule effectors.

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“…FACS analysis of ASAP-transfected U-2 OS cells showed Ϸ40% in G 2 ͞M compared to 17% in the mock control (data not shown). We then immunostained ASAP and the GT335 antigen, a well characterized marker of centrioles, by using a monoclonal antibody directed against glutamylated tubulin (17). Multinucleated cells showed centrosome amplification suggestive of cytokinesis failure (Fig.…”

Section: Molecular Characterization Of Asapmentioning

confidence: 99%

ASAP, a human microtubule-associated protein required for bipolar spindle assembly and cytokinesis

Saffin

Venoux

Prigent

et al. 2005

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

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We have identified a unique human microtubule-associated protein (MAP) named ASAP for ASter-Associated Protein. ASAP localizes to microtubules in interphase, associates with the mitotic spindle during mitosis, localizes to the central body during cytokinesis and directly binds to purified microtubules by its COOHterminal domain. Overexpression of ASAP induces profound bundling of cytoplasmic microtubules in interphase cells and aberrant monopolar spindles in mitosis. Depletion of ASAP by RNA interference results in severe mitotic defects: it provokes aberrant mitotic spindle, delays mitotic progression, and leads to defective cytokinesis or cell death. These results suggest a crucial role for ASAP in the organization of the bipolar mitotic spindle, mitosis progression, and cytokinesis and define ASAP as a key factor for proper spindle assembly. mitosis D ivision of the cell requires coordination between chromosome segregation by a bipolar microtubule (MT)-based structure, the mitotic spindle, and cleavage of the cell by the cytokinetic apparatus. The transition from interphase to mitosis or meiosis is accompanied by a dramatic reorganization of the MT cytoskeleton. The assembly of bipolar spindles is preceded by the movement of centrosomes toward opposite poles of the cell, where these structures function as nucleation sites for MT polymerization (1-3). Spindle assembly and chromosome segregation require MT motor proteins including kinesin-like proteins and cytoplasmic dynein, nonmotor MT-associated proteins (MAPs) required for the regulation of MT dynamics and other molecules, including the small GTPase Ran involved in MT polymerization during mitosis (2, 3). Proper assembly and function of the bipolar spindle is essential for genomic stability (1), and identification of key factors involved in this process as well as knowledge of their regulation are crucial.To ensure high-fidelity DNA transmission during cell division, both chromosome segregation and cytokinesis must be tightly coordinated. Cytokinesis is accomplished by the contraction of an acto-myosin ring that leads to daughter cell separation at the midbody (4). A number of studies have suggested that the temporal and spatial organization of the cytokinetic machine is under the control of the mitotic spindle (5). The spindle midzone composed of highly bundled MTs, originating from the opposite poles, plays an essential role in the initiation and completion of cell cleavage, and is the binding site for a number of proteins that play a part in cytokinesis (6). Among these proteins are passenger proteins (7-9), protein kinases (10), MT motor proteins (11, 12), and MAPs (13). However, the mechanism of central spindle assembly, the molecular basis for maintenance of the midzone MT bundle and the functional roles of these midzone-associated proteins are still largely unknown. Thus, identification of previously undescribed factors involved in both mitosis and cytokinesis may shed light on these different mechanisms.In this paper, we report the identification of...

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Glutamylation of centriole and cytoplasmic tubulin in proliferating non-neuronal cells

Cited by 143 publications

References 44 publications

Protein 4.1R, a Microtubule-associated Protein Involved in Microtubule Aster Assembly in Mammalian Mitotic Extract

Protein 4.1R, a Microtubule-associated Protein Involved in Microtubule Aster Assembly in Mammalian Mitotic Extract

The Tubulin Code

ASAP, a human microtubule-associated protein required for bipolar spindle assembly and cytokinesis

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