Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis (original) (raw)
Related papers
Function and regulation of Maskin, a TACC family protein, in microtubule growth during mitosis
The Journal of Cell Biology, 2005
he Xenopus protein Maskin has been previously identified and characterized in the context of its role in translational control during oocyte maturation. Maskin belongs to the TACC protein family. In other systems, members of this family have been shown to localize to centrosomes during mitosis and play a role in microtubule stabilization. Here we have examined the putative role of Maskin in spindle assembly and centrosome aster formation in the Xenopus egg extract system. Depletion and reconstitution experiments indicate that Maskin T plays an essential role for microtubule assembly during M-phase. We show that Maskin interacts with XMAP215 and Eg2, the Xenopus Aurora A kinase in vitro and in the egg extract. We propose that Maskin and XMAP215 cooperate to oppose the destabilizing activity of XKCM1 therefore promoting microtubule growth from the centrosome and contributing to the determination of microtubule steady-state length. Further more, we show that Maskin localization and function is regulated by Eg2 phosphorylation.
Biological Chemistry, 2000
During the mitotic division cycle, cells pass through an extensive microtubule rearrangement process where microtubules forming the mitotic spindle apparatus are dynamically instable. Several centrosomal-and microtubule-associated proteins are involved in the regulation of microtubule dynamics and stability during mitosis. Here, we focus on members of the transforming acidic coiled coil (TACC) family of centrosomal adaptor proteins, in particular TACC3, in which their subcellular localization at the mitotic spindle apparatus is controlled by Aurora-A kinase-mediated phosphorylation. At the effector level, several TACC-binding partners have been identified and characterized in greater detail, in particular, the microtubule polymerase XMAP215/ch-TOG/CKAP5 and clathrin heavy chain (CHC). We summarize the recent progress in the molecular understanding of these TACC3 protein complexes, which are crucial for proper mitotic spindle assembly and dynamics to prevent faulty cell division and aneuploidy. In this regard, the (patho)biological role of TACC3 in development and cancer will be discussed.
Msps/XMAP215 interacts with the centrosomal protein D-TACC to regulate microtubule behaviour
Nature cell biology, 2001
The XMAP215/ch-TOG/Msps family of microtubule-associated proteins (MAPs) promote microtubule growth in vitro and are concentrated at centrosomes in vivo. We show here that Msps (mini-spindles protein) interacts with the centrosomal protein D-TACC, and that this interaction strongly influences microtubule behaviour in Drosophila embryos. If D-TACC levels are reduced, Msps does not concentrate at the centrosomes efficiently and the centrosomal microtubules appear to be destabilized. If D-TACC levels are increased, both D-TACC and Msps accumulate around the centrosomes/spindle poles, and the centrosomal microtubules appear to be stabilized. We show that the interaction between D-TACC and Msps is evolutionarily conserved. We propose that D-TACC and Msps normally cooperate to stabilize centrosomal microtubules by binding to their minus ends and binding to their plus ends as they grow out from the centrosome.
The TACC proteins: TACC-ling microtubule dynamics and centrosome function
Trends in Cell Biology, 2008
A major quest in cell biology is to understand the molecular mechanisms underlying the high plasticity of the microtubule network at different stages of the cell cycle, and during and after differentiation. Initial reports described the centrosomal localization of proteins possessing transforming acidic coiled-coil (TACC) domains. This discovery prompted several groups to examine the role of TACC proteins during cell division, leading to indications that they are important players in this complex process in different organisms. Here, we review the current understanding of the role of TACC proteins in the regulation of microtubule dynamics, and we highlight the complexity of centrosome function.
TACC3 protein regulates microtubule nucleation by affecting γ-tubulin ring complexes
The Journal of biological chemistry, 2014
Centrosome-mediated microtubule nucleation is essential for spindle assembly during mitosis. Although γ-tubulin complexes have primarily been implicated in the nucleation process, details of the underlying mechanisms remain poorly understood. Here, we demonstrated that a member of the human transforming acidic coiled-coil (TACC) protein family, TACC3, plays a critical role in microtubule nucleation at the centrosome. In mitotic cells, TACC3 knockdown substantially affected the assembly of microtubules in the astral region and impaired microtubule nucleation at the centrosomes. The TACC3 depletion-induced mitotic phenotype was rescued by expression of the TACC3 C terminus predominantly consisting of the TACC domain, suggesting that the TACC domain plays an important role in microtubule assembly. Consistently, experiments with the recombinant TACC domain of TACC3 demonstrated that this domain possesses intrinsic microtubule nucleating activity. Co-immunoprecipitation and sedimentation...
The Journal of cell biology, 2003
A mitosis-specific Aurora-A kinase has been implicated in microtubule organization and spindle assembly in diverse organisms. However, exactly how Aurora-A controls the microtubule nucleation onto centrosomes is unknown. Here, we show that Aurora-A specifically binds to the COOH-terminal domain of a Drosophila centrosomal protein, centrosomin (CNN), which has been shown to be important for assembly of mitotic spindles and spindle poles. Aurora-A and CNN are mutually dependent for localization at spindle poles, which is required for proper targeting of gamma-tubulin and other centrosomal components to the centrosome. The NH2-terminal half of CNN interacts with gamma-tubulin, and induces cytoplasmic foci that can initiate microtubule nucleation in vivo and in vitro in both Drosophila and mammalian cells. These results suggest that Aurora-A regulates centrosome assembly by controlling the CNN's ability to targeting and/or anchoring gamma-tubulin to the centrosome and organizing mic...
TAC-1 and ZYG-9 Form a Complex that Promotes Microtubule Assembly in C. elegans Embryos
Current Biology, 2003
are present in all eukaryotes, including H. sapiens (ch-TOG), D. melanogaster (Msps), and C. elegans (ZYG-9) Switzerland (see [6] for a review). Inactivation of XMAP215 family members typically results in short microtubules and aberrant spindle assembly, although whether this is due Summary to impaired growth at the plus ends has not been determined in vivo [7-10]. Intriguingly, members of the Background: Modulation of microtubule dynamics is XMAP215 protein family are enriched at centrosomes crucial for proper cell division. While a large body of and spindle poles, rather than at the plus ends of microwork has made important contributions to our undertubules. Recent evidence indicates that XMAP215 can standing of the mechanisms governing microtubule dyalso promote microtubule depolymerization in Xenopus namics in vitro, much remains to be learned about how egg extracts [11]. Although this activity appears to be these mechanisms operate in vivo. specific to plus ends, it has been suggested that Results: We identified TAC-1 as the sole TACC (Trans-XMAP215 at centrosomes may help depolymerize miforming Acidic Coiled Coil) protein in C. elegans. TAC-1 crotubules that are misoriented with their minus end consists essentially of a TACC domain, in contrast to facing out [11]. the much larger members of this protein family in other Work in Drosophila has led to the identification of species. We find that tac-1 is essential for pronuclear D-TACC (Transforming and Acidic Coiled-Coil) as a key migration and spindle elongation in one-cell-stage C. regulator of Msps function [12, 13]. D-TACC is enriched elegans embryos. Using an in vivo FRAP-based assay, at centrosomes and physically interacts with Msps. we establish that inactivation of tac-1 results in defective Moreover, Msps enrichment at centrosomes is diminmicrotubule assembly. TAC-1 is present in the cytoished when D-TACC levels are reduced [12]. These findplasm and is enriched at centrosomes in a cell cycleings have led to the proposal that D-TACC plays a crucial dependent manner. Centrosomal localization is inderole in recruiting or maintaining Msps at centrosomes pendent of microtubules but requires the activity of and thus helps it bind to microtubule plus ends as they ␥-tubulin and the Aurora-A kinase AIR-1. By conducting grow out from centrosomes. Compatible with this FRAP analysis in embryos expressing GFP-TAC-1, we model, imaging of D-TACC-GFP and Msps-GFP refind that centrosomal TAC-1 exchanges rapidly with the vealed small dots oscillating to and from the centrocytoplasmic pool. Importantly, we establish that TAC-1 somes [12]. Whether a requirement for TACC proteins physically interacts with ZYG-9, a microtubule-associin recruiting or maintaining XMAP215 family members ated protein (MAP) of the XMAP215 family, both in vitro at centrosomes is evolutionarily conserved, or whether and in vivo. Furthermore, we also uncover that TAC-1 D-TACC may play a more general role in Msps metaboand ZYG-9 stabilize each other in C. elegans embryos. lism, remains to be clarified. Conclusions: Our findings identify TAC-1 as a core The early C. elegans embryo is particularly well suited structural and functional member of the evolutionarily for a high-resolution analysis of the spatial and temporal conserved TACC family of proteins and suggest that control of microtubule dynamics in living organisms. mutual stabilization between TACC and XMAP215 pro-As is the case for other eukaryotes, the C. elegans teins is a key feature ensuring microtubule assembly XMAP215 family member ZYG-9 is required for microtuin vivo. bule-dependent processes: embryos derived from mothers lacking zyg-9 function have short astral microtubules
XTACC3–XMAP215 association reveals an asymmetric interaction promoting microtubule elongation
Nature Communications, 2014
chTOG is a conserved microtubule polymerase that catalyses the addition of tubulin dimers to promote microtubule growth. chTOG interacts with TACC3, a member of the transforming acidic coiled-coil (TACC) family. Here we analyse their association using the Xenopus homologues, XTACC3 (TACC3) and XMAP215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215. Our data suggest that one TD and two XMAP215 molecules associate to form a four-helix coiled-coil complex. A hybrid methods approach was used to define the precise regions of the TACC heptad repeat and the XMAP215 C terminus required for assembly and functioning of the complex. We show that XTACC3 can induce the recruitment of larger amounts of XMAP215 by increasing its local concentration, thereby promoting efficient microtubule elongation during mitosis.