Kinoshita K, Noetzel TL, Pelletier L, Mechtler K, Drechsel DN, Schwager A et al.. Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis. J Cell Biol 170: 1047-1055

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), 01307 Dresden, Germany.
The Journal of Cell Biology (Impact Factor: 9.83). 10/2005; 170(7):1047-55. DOI: 10.1083/jcb.200503023
Source: PubMed


Centrosomes act as sites of microtubule growth, but little is known about how the number and stability of microtubules emanating from a centrosome are controlled during the cell cycle. We studied the role of the TACC3-XMAP215 complex in this process by using purified proteins and Xenopus laevis egg extracts. We show that TACC3 forms a one-to-one complex with and enhances the microtubule-stabilizing activity of XMAP215 in vitro. TACC3 enhances the number of microtubules emanating from mitotic centrosomes, and its targeting to centrosomes is regulated by Aurora A-dependent phosphorylation. We propose that Aurora A regulation of TACC3 activity defines a centrosome-specific mechanism for regulation of microtubule polymerization in mitosis.

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Available from: Laurence Pelletier, Oct 06, 2015
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    • "We observed that TACC1 and TACC3 have the highest expression in early stage embryos, whereas levels decline throughout development. Note that the particularly high expression of TACC3 may reflect the prominent mitotic role for this protein [Gergely et al., 2000; Kinoshita et al., 2005; Yao et al., 2007], but its constant presence in later stages would indicate an additional continued role throughout embryonic development. TACC1 appears to be expressed similarly to TACC3, although its expression is not as strong in the early embryo. "
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    ABSTRACT: Microtubule plus-end dynamics are regulated by a family of proteins called plus end-tracking proteins (+TIPs). We recently demonstrated that the transforming acidic coiled-coil (TACC) domain family member, TACC3, can function as a +TIP to regulate microtubule dynamics in Xenopus laevis embryonic cells. Although it has been previously reported that TACC3 is the only TACC family member that exists in Xenopus, our examination of its genome determined that Xenopus, like all other vertebrates, contains three TACC family members. Here, we investigate the localization and function of Xenopus TACC1, the founding member of the TACC family. We demonstrate that it can act as a +TIP to regulate microtubule dynamics, and that the conserved C-terminal TACC domain is required for its localization to plus-ends. We also show that, in Xenopus embryonic mesenchymal cells, TACC1 and TACC3 are each required for maintaining normal microtubule growth speed but exhibit some functional redundancy in the regulation of microtubule growth lifetime. Given the conservation of TACC1 in Xenopus and other vertebrates, we propose that Xenopus laevis is a useful system to investigate unexplored cell biological functions of TACC1 and other TACC family members in the regulation of microtubule dynamics. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Cytoskeleton 05/2015; 72(5). DOI:10.1002/cm.21224 · 3.12 Impact Factor
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    • "It has been suggested that a primary function of TACC3 is to recruit the microtubule polymerase XMAP215 to the centrosome (Peset and Vernos, 2008). The interaction between TACC3 and XMAP215 has been well documented in multiple systems (Lee et al., 2001; Kinoshita et al., 2005; O'Brien et al., 2005; Peset et al., 2005), where it is apparent that TACC3 localizes XMAP215 to the centrosome and that normal mitotic spindle assembly requires their interaction. However, despite the well-known localization of XMAP215 at growing MT plus ends (Brouhard et al., 2008), it has been unclear whether vertebrate TACC3 interacts with XMAP215 specifically at plus ends during interphase. "
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    ABSTRACT: Microtubule plus-end dynamics are regulated by a conserved family of proteins called 'plus-end-tracking proteins' (+TIPs). Yet, it is still unclear how various +TIPs interact with each other and with plus-ends to control microtubule behavior. The centrosome-associated protein TACC3, a member of the transforming acidic coiled coil (TACC) domain family, has been previously implicated in regulating several aspects of microtubule dynamics. However, TACC3 has not been shown to function as a +TIP in vertebrates. Here, we show that TACC3 promotes axon outgrowth and regulates microtubule dynamics by increasing microtubule plus-end velocities in vivo. We also demonstrate that TACC3 acts as a +TIP in multiple embryonic cell types, and that this requires the conserved C-terminal TACC domain. Using high-resolution live-imaging data of tagged +TIPs, we reveal that TACC3 localizes to the extreme microtubule plus-end, where it lies distal to the microtubule polymerization marker, EB1, and directly overlaps with the microtubule polymerase, XMAP215. TACC3 also plays a role in regulating XMAP215 stability and localizing XMAP215 to microtubule plus-ends. Together, our results implicate TACC3 as a +TIP that functions with XMAP215 to regulate microtubule plus-end dynamics.
    Molecular Biology of the Cell 09/2014; 25(21). DOI:10.1091/mbc.E14-06-1121 · 4.47 Impact Factor
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    • "To stabilize the centrosomal microtubules, AurA phosphorylates the centrosomal adaptor TACC3 and, in a clathrin-dependent manner, targets it exclusively to the mitotic centrosome (Fu et al., 2010), where it interacts with the microtubule-stabilizing factor ch-TOG (also known as CKAP5). The formation of the TACC3–ch-TOG complex enhances the affinity of ch-TOG for microtubules, which, in turn functions to increase the stability of centrosomal microtubules by counteracting the activity of the microtubule-depolymerizing kinesin MCAK (also known as KIF2C) (Barros et al., 2005; Kinoshita et al., 2005; Peset et al., 2005). Taken together, these findings emphasize the importance of the centrosome in regulating aspects of cell cycle progression and spindle assembly that are controlled by AurA (Fig. 3). "
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    ABSTRACT: The centrosome acts as the major microtubule-organizing center (MTOC) for cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate cells. It duplicates only once per cell cycle in a highly spatiotemporally regulated manner. When the cell undergoes mitosis, the duplicated centrosomes separate to define spindle poles and monitor the assembly of the bipolar mitotic spindle for accurate chromosome separation and the maintenance of genomic stability. However, centrosome abnormalities occur frequently and often lead to monopolar or multipolar spindle formation, which results in chromosome instability and possibly tumorigenesis. A number of studies have begun to dissect the role of mitotic kinases, including NIMA-related kinases (Neks), cyclin-dependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in regulating centrosome duplication, separation and maturation and subsequent mitotic spindle assembly during cell cycle progression. In this Commentary, we review the recent research progress on how these mitotic kinases are coordinated to couple the centrosome cycle with the cell cycle, thus ensuring bipolar mitotic spindle fidelity. Understanding this process will help to delineate the relationship between centrosomal abnormalities and spindle defects.
    Journal of Cell Science 08/2014; 127(19). DOI:10.1242/jcs.151753 · 5.43 Impact Factor
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