Length-dependent anisotropic scaling of spindle shape

Young, Sarah Jane; Besson, Sébastien; Welburn, Julie

doi:10.1242/bio.201410363

Cited by 21 publications

(21 citation statements)

References 49 publications

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“…In this article, we refine our established model and use it to explore the possible connection between the size scaling in mitotic spindles and the SAC silencing signal. The model results show that robust and timely SAC silencing requires a relationship between spindle length and spindle width similar to that observed in experiments (11,12). More importantly, the same functional requirements for SAC impose constraints on the spindle size given the cell size, which remarkably recapitulates the observed universal scaling relationship between the spindle and cell sizes across the Metazoa (5).…”

Section: Introductionsupporting

confidence: 71%

“…In other words, conditions for proper SAC silencing could constrain the relationship between spindle length and spindle width. The findings suggest that the observed allometric scaling between spindle length and spindle width (11,12) might be shaped by the functional requirement for proper SAC signaling.…”

Section: Allometric Relationship Between Spindle Length and Widthmentioning

confidence: 91%

“…In sum, the spindle pole signal largely depends on the overall microtubule density in the spindle, but the jump ratio, which relies on the concentration of streaming proteins available to the unattached kinetochores, is regulated by the size-dependent changes in the microtubule density profile in the spindle. Altogether, robust, timely SAC silencing might have functionally shaped the observed allometric relationship between spindle length and width (11,12).…”

Section: A B C D Ementioning

confidence: 99%

“…The mitotic spindle can vary from submicron in yeast to~60 mm in Xenopus eggs, whereas the cells that house these spindles may range from a few microns up to~1 mm (5). Recent experiments reveal a striking relationship between the spindle size and cell size (5)(6)(7)(8)(9)(10)(11), as well as between various dimensions of the spindle (e.g., spindle width, spindle length, spindle pole size) (7,(11)(12)(13)(14). Most intriguingly, the spindle size scales linearly with the cell size up to a certain limit; and such a biphasic scaling relationship, as well as the critical cell size and spindle size for the biphasic transition, appear surprisingly consistent across metazoan species (5,8,10).…”

Section: Introductionmentioning

confidence: 99%

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Spindle Size Scaling Contributes to Robust Silencing of Mitotic Spindle Assembly Checkpoint

Chen

Liu

2016

Biophysical Journal

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Chromosome segregation during mitosis hinges on proper assembly of the microtubule spindle that establishes bipolar attachment to each chromosome. Experiments demonstrate allometry of mitotic spindles and a universal scaling relationship between spindle size and cell size across metazoans, which indicates a conserved principle of spindle assembly at play during evolution. However, the nature of this principle is currently unknown. Researchers have focused on deriving the mechanistic underpinning of the size scaling from the mechanical aspects of the spindle assembly process. In this work we take a different standpoint and ask: What is the size scaling for? We address this question from the functional perspectives of spindle assembly checkpoint (SAC). SAC is the critical surveillance mechanism that prevents premature chromosome segregation in the presence of unattached or misattached chromosomes. The SAC signal gets silenced after and only after the last chromosome-spindle attachment in mitosis. We previously established a model that explains the robustness of SAC silencing based on spindle-mediated spatiotemporal regulation of SAC proteins. Here, we refine the previous model, and find that robust and timely SAC silencing entails proper size scaling of mitotic spindle. This finding provides, to our knowledge, a novel, function-oriented angle toward understanding the observed spindle allometry, and the universal scaling relationship between spindle size and cell size in metazoans. In a broad sense, the functional requirement of robust SAC silencing could have helped shape the spindle assembly mechanism in evolution.

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Section: Introductionsupporting

confidence: 71%

Section: Allometric Relationship Between Spindle Length and Widthmentioning

confidence: 91%

Section: A B C D Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spindle Size Scaling Contributes to Robust Silencing of Mitotic Spindle Assembly Checkpoint

Chen

Liu

2016

Biophysical Journal

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“…This occurs without changing MT density, lifetime, and spindle shape, suggesting that spindle size is determined separately and by mass balance (94). Similarly, the factors that determine spindle shape are not well established, and recent studies in human cells and C. elegans have shown that spindle shape scales anisotropically with spindle length and chromosome number (95,96).…”

Section: Assembly and Scaling Of Self-organized Microtubule Structuresmentioning

confidence: 99%

Building the Microtubule Cytoskeleton Piece by Piece

Alfaro-Aco

Petry

2015

Journal of Biological Chemistry

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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 (...

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Reciprocal regulation of Aurora kinase A and ATIP3 in the control of metaphase spindle length

Nehlig

Seiler

Steblyanko

et al. 2020

Cell. Mol. Life Sci.

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Maintaining the integrity of the mitotic spindle in metaphase is essential to ensure normal cell division. We show here that depletion of microtubule-associated protein ATIP3 reduces metaphase spindle length. Mass spectrometry analyses identiied the microtubule minus-end depolymerizing kinesin Kif2A as an ATIP3 binding protein. We show that ATIP3 controls metaphase spindle length by interacting with Kif2A and its partner Dda3 in an Aurora kinase A-dependent manner. In the absence of ATIP3, Kif2A and Dda3 accumulate at spindle poles, which is consistent with reduced poleward microtubule lux and shortening of the spindle. ATIP3 silencing also limits Aurora A localization to the poles. Transfection of GFP-Aurora A, but not kinase-dead mutant, rescues the phenotype, indicating that ATIP3 maintains Aurora A activity on the poles to control Kif2A targeting and spindle size. Collectively, these data emphasize the pivotal role of Aurora kinase A and its mutual regulation with ATIP3 in controlling spindle length.

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Length-dependent anisotropic scaling of spindle shape

Cited by 21 publications

References 49 publications

Spindle Size Scaling Contributes to Robust Silencing of Mitotic Spindle Assembly Checkpoint

Spindle Size Scaling Contributes to Robust Silencing of Mitotic Spindle Assembly Checkpoint

Building the Microtubule Cytoskeleton Piece by Piece

Reciprocal regulation of Aurora kinase A and ATIP3 in the control of metaphase spindle length

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