The Distribution of Active Force Generators Controls Mitotic Spindle Position

Grill, Stephan W.; Howard, Jonathon; Schäffer, Erik; Stelzer, Ernst H. K.; Hyman, Anthony A.

doi:10.1126/science.1086560

Cited by 352 publications

(393 citation statements)

References 24 publications

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“…The laser ablation experiments were performed using a highly focused ultraviolet laser beam and observed using differential interference contrast (DIC) and spinning-disk microscopy as described 22 , except that a Melles Griot ArIon Laser (488 nm, 100 mW) laser was used for fluorescence imaging. All ablations were performed in DIC optics.…”

Section: Methodsmentioning

confidence: 99%

A cytokinesis furrow is positioned by two consecutive signals

Bringmann

Hyman

2005

Nature

207

201

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Section: Methodsmentioning

confidence: 99%

A cytokinesis furrow is positioned by two consecutive signals

Bringmann

Hyman

2005

Nature

207

201

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“…Such experiments illustrate the existence of a mechanical link between the spindle and specialized cortical regions [4,5]. Laser microsurgery experiments in Fusarium solani or C. elegans suggested that this link corresponds to astral microtubules connecting the spindle poles with the cell cortex [6,7,8,9,10 ]. Although not the focus of this review, there are instances where pulling forces are exerted along the length of astral microtubules instead of at their plusend located at the cell cortex [11,12,13].…”

mentioning

confidence: 94%

Mechanisms of spindle positioning: cortical force generators in the limelight

Kotak

Gönczy

2013

Current Opinion in Cell Biology

156

138

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Correct positioning of the spindle governs placement of the cytokinesis furrow and thus plays a crucial role in the partitioning of fate determinants and the disposition of daughter cells in a tissue. Converging evidence indicates that spindle positioning is often dictated by interactions between the plus-end of astral microtubules that emanate from the spindle poles and an evolutionary conserved cortical machinery that serves to pull on them. At the heart of this machinery lies a ternary complex (LIN-5/GPR-1/2/Ga in Caenorhabditis elegans and NuMA/LGN/Gai in Homo sapiens) that promotes the presence of the motor protein dynein at the cell cortex. In this review, we discuss how the above components contribute to spindle positioning and how the underlying mechanisms are precisely regulated to ensure the proper execution of this crucial process in metazoan organisms IntroductionThe mitotic spindle is a diamond-shaped microtubulebased structure that faithfully segregates sister chromatids during cell division. Several types of microtubules emanate from the spindle poles, including astral microtubules that reach out to the actin rich cortex located beneath the plasma membrane ( Figure 1a). Pulling forces exerted on the plus-end of astral microtubules at the cell cortex are critical for accurately positioning the spindle with respect to cell-intrinsic or cell-extrinsic spatial cues. In turn, correct spindle positioning dictates placement of the cytokinesis furrow and is thus essential for determining the relative size and spatial disposition of the resulting daughter cells [2]. Accurate spindle positioning also ensures that cell fate determinants are appropriately segregated into daughter cells during development and in stem cell lineages [3].What features of the cell cortex allow interactions with astral microtubules to orchestrate spindle positioning? Specialized cortical sites are key. Their importance has been suggested for instance by elegant experiments in Chaetopterus oocytes, in which the meiotic spindle pulled away from its cortical attachment site using a micro-needle returns to that location once released (Figure 1b). Such experiments illustrate the existence of a mechanical link between the spindle and specialized cortical regions [4,5]. Laser microsurgery experiments in Fusarium solani or C. elegans suggested that this link corresponds to astral microtubules connecting the spindle poles with the cell cortex [6,7,8,9,10 ]. Although not the focus of this review, there are instances where pulling forces are exerted along the length of astral microtubules instead of at their plusend located at the cell cortex [11,12,13]. Work in several systems in recent years has increased our understanding of the basic principles governing spindle positioning and identified core molecular players and aspects of their mechanism of action. In this brief review, we will focus on cortically driven spindle positioning in one-cell C. elegans embryos and mammalian cells in culture. In doing so, we will discuss the nature of the t...

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“…First, mechanical material properties play a key role in the control of numerous cellular processes such as cell shape changes [1], cell locomotion [2], adhesion [3] or cell division [4] by mechanical forces. Second, local forces can control the cellular architecture in a subtle way, for instance through the activation of small GTPases of the rho-family [5] which can result in rapid (sub-second) reorganizations of the actin network [6], including the formation of stress fibres [7], the activation of micro-muscles or the growth of cellular protrusions, such as philipodia [8] or axons [9].…”

Section: Introductionmentioning

confidence: 99%

Active mechanical stabilization of the viscoplastic intracellular space of Dictyostelia cells by microtubule–actin crosstalk

Heinrich

Sackmann²

2006

Acta Biomaterialia

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The micro-viscoelasticity of the intracellular space of Dictyostelium discoideum cells is studied by evaluating the intracellular transport of magnetic force probes and their viscoelastic responses to force pulses of 20-700 pN. The role of the actin cortex, the microtubule (MT) aster and their crosstalk is explored by comparing the behaviour of wild-type cells, myosin II null mutants, latrunculin A and benomyl treated cells. The MT coupled beads perform irregular local and long range directed motions which are characterized by measuring their velocity distributions (P(v)). The correlated motion of the MT and the centrosome are evaluated by microfluorescence of GFP-labelled MTs. P(v) can be represented by log-normal distributions with long tails and it is determined by random sweeping motions (v $ 0.5 lm/s) of the MTs (caused by tangential forces on the filament ends coupled to the actin cortex) and by intermittent bead transports parallel to the MTs (v max $ 1.5 lm/s). The tails are due to spontaneous filament deflections (with speeds up to 10 lm/s) attributed to pre-stressing of the MT by local cortical tensions, generated by dynactin motors generating plus-end directed forces in the MTs. The viscoelastic responses are strongly non-linear and are mostly directed opposite or perpendicular to the force, showing that the cytoplasm behaves as an active viscoplastic body with time and force dependent drag coefficients. Nano-Newton loads exerted on the soft MT are balanced by traction forces arising at the MT ends coupled to the actin cortex and the centrosome, respectively. The mechanical coupling between the soft microtubules and the viscoelastic actin cortex provides cells with high mechanical stability despite the softness of the cytoplasm.

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The Distribution of Active Force Generators Controls Mitotic Spindle Position

Cited by 352 publications

References 24 publications

A cytokinesis furrow is positioned by two consecutive signals

A cytokinesis furrow is positioned by two consecutive signals

Mechanisms of spindle positioning: cortical force generators in the limelight

Active mechanical stabilization of the viscoplastic intracellular space of Dictyostelia cells by microtubule–actin crosstalk

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