K-fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly

Meunier, Sylvain; Vernos, Isabelle

doi:10.1038/ncb2372

Cited by 90 publications

(128 citation statements)

References 52 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…These data provide a molecular link between the chromosomal MTs and the K-fibers that goes beyond previous observations of the formation of acentrosomal MTs at the kinetochores (Khodjakov et al, 2003;Maiato et al, 2004). Interestingly, the distinct spindle MT subclasses have distinct dynamic properties, (Rizk et al, 2009), and functional studies have shown that MCRS1 could have a role in the regulation of Kfiber minus-end stability (Meunier and Vernos, 2011).…”

Section: Kidsupporting

confidence: 51%

“…Importin-b (Meunier and Vernos, 2011) Binds and protects chromosomal MT minusends (Meunier and Vernos, 2011) n.d.…”

Section: Mcrs1mentioning

confidence: 99%

“…The combination of MTs from the three pathways could therefore allow the timely assembly of the bipolar spindle and allow mitosis to progress successfully. The recent identification of microspherule protein 1 (MCRS1) as a SAF (Meunier and Vernos, 2011) suggests that there is a possibility that the different MTs are not equivalent but differ in terms of dynamics and molecular composition. The table shows the requirements of the components of the c-TuSC, c-TuRC and c-TuRC-associated proteins in the three MT assembly pathways (centrosomes, MTs and chromosomes).…”

Section: Kidmentioning

confidence: 99%

See 2 more Smart Citations

Microtubule assembly during mitosis – from distinct origins to distinct functions?

Meunier

Vernos

2012

Journal of Cell Science

Self Cite

125

View full text Add to dashboard Cite

SummaryThe mitotic spindle is structurally and functionally defined by its main component, the microtubules (MTs). The MTs making up the spindle have various functions, organization and dynamics: astral MTs emanate from the centrosome and reach the cell cortex, and thus have a major role in spindle positioning; interpolar MTs are the main constituent of the spindle and are key for the establishment of spindle bipolarity, chromosome congression and central spindle assembly; and kinetochore-fibers are MT bundles that connect the kinetochores with the spindle poles and segregate the sister chromatids during anaphase. The duplicated centrosomes were long thought to be the origin of all of these MTs. However, in the last decade, a number of studies have contributed to the identification of noncentrosomal pathways that drive MT assembly in dividing cells. These pathways are now known to be essential for successful spindle assembly and to participate in various processes such as K-fiber formation and central spindle assembly. In this Commentary, we review the recent advances in the field and discuss how different MT assembly pathways might cooperate to successfully form the mitotic spindle.

show abstract

Section: Kidsupporting

confidence: 51%

“…Importin-b (Meunier and Vernos, 2011) Binds and protects chromosomal MT minusends (Meunier and Vernos, 2011) n.d.…”

Section: Mcrs1mentioning

confidence: 99%

Section: Kidmentioning

confidence: 99%

See 1 more Smart Citation

Microtubule assembly during mitosis – from distinct origins to distinct functions?

Meunier

Vernos

2012

Journal of Cell Science

Self Cite

125

View full text Add to dashboard Cite

show abstract

“…In mammalian somatic cells, Ran GTPase activity promotes microtubule nucleation at kinetochores (33), and Ran effectors such as microspherule protein 1 and γ-TuRC also function in K fibers (34,35). As TACC3 is also a target of the Ran GTPase system (20), it may coordinate with Ran to regulate acentrosomal microtubules for kinetochore capture.…”

Section: Tacc3-dependent Acentrosomal Microtubule Nucleation Is Requimentioning

confidence: 99%

Self-assembly and sorting of acentrosomal microtubules by TACC3 facilitate kinetochore capture during the mitotic spindle assembly

Chen

Wang

et al. 2013

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

View full text Add to dashboard Cite

Kinetochore capture by dynamic kinetochore microtubule fibers (K fibers) is essential for proper chromosome alignment and accurate distribution of the replicated genome during cell division. Although this capture process has been extensively studied, the mechanisms underlying the initiation of this process and the proper formation of the K fibers remain largely unknown. Here we show that transforming acidic coiled-coil-containing protein 3 (TACC3) is essential for kinetochore capture and proper K-fiber formation in HeLa cells. To observe the assembly of acentrosomal microtubules more clearly, the cells were released from higher concentrations of nocodazole into zero or lower concentrations. We find that small acentrosomal TACC3-microtubule aster formation near the kinetochores and binding of the asters with the kinetochores are the initial steps of the kinetochore capture by the acentrosomal microtubules, and that the sorting of kinetochore-captured acentrosomal microtubules with centrosomal microtubules leads to the capture of kinetochore by centrosomal microtubules from both spindle poles. We demonstrate that the sorting of the TACC3-associated microtubules with the centrosomal microtubules is a crucial process for spindle assembly and chromosome movement. These findings, which are also supported in the unperturbed mitosis without nocodazole, reveal a critical TACC3-dependent acentrosomal microtubule nucleation and sorting process to regulate kinetochore-microtubule connections and provide deep insight into the mechanisms of mitotic spindle assembly and chromosome alignment.T o ensure proper segregation of the chromosomes into its two daughter cells during proliferation, the chromosomes of a mother cell must be captured by its assembling mitotic spindle through attachment of the chromosome kinetochores and the dynamic spindle microtubules (1). A "search-and-capture" model was proposed long ago, in which the dynamic spindle microtubules nucleated from the centrosomes search for and capture the chromosome kinetochores (2). Previous studies showed that the kinetochores are initially captured by the spindle-polenucleated microtubules with their lateral side (3, 4). Once captured, the kinetochores with their chromosomes are transported along the microtubules toward a spindle pole, and the microtubules shrink at their plus ends until the establishment of the end-on attachment (4, 5). However, this model is insufficient to explain the initial connection of the kinetochore and the spindle microtubules in the centrosome-independent spindle assembly process. Recent studies in Xenopus extracts indicated that microtubules are nucleated near the chromosomes and self-organize into a spindle (6). A new model for acentrosomal spindle assembly has been raised in mouse oocytes, in which self-organized microtubule organizing centers (MTOCs) replace the centrosome function (7). The somatic cells may also use the centrosome-independent pathway for their spindle assembly (8-10). In Drosophila cells, the centrosome-independent assem...

show abstract

“…In an analogous manner, MCAK interacts with the EB1-dependent plus-tip tracking kinesin 8 Kif18b, and this interaction is required for robust MT depolymerization in cells (52,53). The specificity of MCAK as a plus-end depolymerase could be further regulated by the minus-end-binding proteins patronin/CAMSAP (54 -56) and MCRS1 (57), which block MCAK activity at the MT minus-end to enhance MT stability (Fig. 2G).…”

Section: Adding Complexity Via ؉ Tipsmentioning

confidence: 95%

Building the Microtubule Cytoskeleton Piece by Piece

Alfaro-Aco

Petry

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

The microtubule (MT) cytoskeleton gives cells their shape, organizes the cellular interior, and segregates chromosomes. These functions rely on the precise arrangement of MTs, which is achieved by the coordinated action of MT-associated proteins (MAPs). We highlight the first and most important examples of how different MAP activities are combined in vitro to create an ensemble function that exceeds the simple addition of their individual activities, and how the Xenopus laevis egg extract system has been utilized as a powerful intermediate between cellular and purified systems to uncover the design principles of selforganized MT networks in the cell. The microtubule (MT)2 cytoskeleton forms the skeletal framework that gives eukaryotic cells their shape and organizes their cytoplasm by positioning organelles, providing tracks for transport, and establishing cell polarity. In an interphase cell, the MT cytoskeleton is also critical for cell motility and a key constituent of cilia and flagella. During cell division, the MT cytoskeleton gets remodeled into a spindle structure that segregates chromosomes. Each of these functions relies on a specific MT architecture, which must be capable of rapid and prolonged change followed by an eventual resumption of a steady state to respond to the cellular environment and morphology changes during growth and differentiation.MTs are made of ␣/␤-tubulin heterodimers, which assemble into a polar, cylindrical structure in the presence of GTP and above the so-called critical concentration in vitro. MT growth phases alternate with swift shrinkage phases (dynamic instability), and their transitions are referred to as catastrophe (switching from growth to shrinkage) and rescue (switching from shrinkage to growth) (1). In cells, a plethora of different MT-associated proteins (MAPs) regulate the MT-inherent abilities of MT nucleation and dynamics ( Fig. 1A) (2). In addition, MT cross-linking proteins connect MTs into networks and molecular motors use MTs as tracks for cargo transport or transport MTs themselves (Fig. 1A). Altogether, different combinations of these four basic groups of MAP activities drive the self-organization of the MT cytoskeleton into discrete three-dimensional patterns (Fig. 1B) (3). Thus, they establish, maintain, and disassemble functional MT structures that are observed on the cellular level.Traditionally, individual MAPs were identified by loss-offunction experiments in cells followed by their detailed in vivo and in vitro characterization. During the past decade, highthroughput genomic and proteomic screens accelerated MAP discovery by cataloging RNAi phenotypes and identifying novel microtubule binders, resulting in comprehensive lists of candidates involved in organizing the MT cytoskeleton in various cell states (4 -7). Now, the challenge is to understand how these MAPs work together to establish the physiological MT architecture of the cell. What specific MAP building blocks can generate the MT networks that shape a dendrite or a polarized epithelial cell (...

show abstract

K-fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly

Cited by 90 publications

References 52 publications

Microtubule assembly during mitosis – from distinct origins to distinct functions?

Microtubule assembly during mitosis – from distinct origins to distinct functions?

Self-assembly and sorting of acentrosomal microtubules by TACC3 facilitate kinetochore capture during the mitotic spindle assembly

Building the Microtubule Cytoskeleton Piece by Piece

Contact Info

Product

Resources

About