Intracellular Transport by an Anchored Homogeneously Contracting F-Actin Meshwork

Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, D-69117, Germany.
Current biology: CB (Impact Factor: 9.57). 03/2011; 21(7):606-11. DOI: 10.1016/j.cub.2011.03.002
Source: PubMed

ABSTRACT Actin-based contractility orchestrates changes in cell shape underlying cellular functions ranging from division to migration and wound healing. Actin also functions in intracellular transport, with the prevailing view that filamentous actin (F-actin) cables serve as tracks for motor-driven transport of cargo. We recently discovered an alternate mode of intracellular transport in starfish oocytes involving a contractile F-actin meshwork that mediates chromosome congression. The mechanisms by which this meshwork contracts and translates its contractile activity into directional transport of chromosomes remained open questions. Here, we use live-cell imaging with quantitative analysis of chromosome trajectories and meshwork velocities to show that the 3D F-actin meshwork contracts homogeneously and isotropically throughout the nuclear space. Centrifugation experiments reveal that this homogeneous contraction is translated into asymmetric, directional transport by mechanical anchoring of the meshwork to the cell cortex. Finally, by injecting inert particles of different sizes, we show that this directional transport activity is size-selective and transduced to chromosomal cargo at least in part by steric trapping or "sieving." Taken together, these results reveal mechanistic design principles of a novel and potentially versatile mode of intracellular transport based on sieving by an anchored homogeneously contracting F-actin meshwork.

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    • "There has been a plethora of excellent reviews on the control of spindle positioning for asymmetric divisions during metazoan development (e.g. Gönczy, 2002; Gönczy, 2008; Knoblich, 2010; Morin and Bellaı¨che, 2011). The aim of this Commentary is to give an overview of the strategies used by cells to orient the spindle, with a specific emphasis on the emerging roles of the actin cytoskeleton. "
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    ABSTRACT: Asymmetric divisions are essential in metazoan development, where they promote the emergence of cell lineages. The mitotic spindle has astral microtubules that contact the cortex, which act as a sensor of cell geometry and as an integrator to orient cell division. Recent advances in live imaging revealed novel pools and roles of F-actin in somatic cells and in oocytes. In somatic cells, cytoplasmic F-actin is involved in spindle architecture and positioning. In starfish and mouse oocytes, newly discovered meshes of F-actin control chromosome gathering and spindle positioning. Because oocytes lack centrosomes and astral microtubules, F-actin networks are key players in the positioning of spindles by transmitting forces over long distances. Oocytes also achieve highly asymmetric divisions, and thus are excellent models to study the roles of these newly discovered F-actin networks in spindle positioning. Moreover, recent studies in mammalian oocytes provide a further understanding of the organisation of F-actin networks and their biophysical properties. In this Commentary, we present examples of the role of F-actin in spindle positioning and asymmetric divisions, with an emphasis on the most up-to-date studies from mammalian oocytes. We also address specific technical issues in the field, namely live imaging of F-actin networks and stress the need for interdisciplinary approaches.
    Journal of Cell Science 01/2014; 127(3). DOI:10.1242/jcs.142711 · 5.43 Impact Factor
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    • "Currently, all the known RanGTP targets are MAPs or their regulators (11). It has been shown in starfish oocytes that chromatin drives local actin polymerization to mediate chromosome congression (41). The MAP NabKin has been identified as a nuclear protein that binds fibrous actin in a RanGTP-dependent manner (42). "
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    ABSTRACT: Faithful action of the mitotic spindle segregates duplicated chromosomes into daughter cells. Perturbations of this process result in chromosome mis-segregation, leading to chromosomal instability and cancer development. Chromosomes are not simply passengers segregated by spindle microtubules but rather play a major active role in spindle assembly. The GTP bound form of the Ran GTPase (RanGTP), produced around chromosomes, locally activates spindle assembly factors. Recent studies have uncovered that chromosomes organize mitosis beyond spindle formation. They distinctly regulate other mitotic events, such as spindle maintenance in anaphase, which is essential for chromosome segregation. Furthermore, the direct function of chromosomes is not only to produce RanGTP but, in addition, to release key mitotic regulators from chromatin. Chromatin-remodeling factors and nuclear pore complex proteins, which have established functions on chromatin in interphase, dissociate from mitotic chromatin and function in spindle assembly or maintenance. Thus, chromosomes actively organize their own segregation using chromatin-releasing mitotic regulators as well as RanGTP.
    Frontiers in Oncology 12/2013; 3:308. DOI:10.3389/fonc.2013.00308
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    • "Actin is an abundant protein present in all eukaryotic cells, and actin polymerization and depolymerization play fundamental roles in biological processes such as cell migration, determining cell shape, vesicle trafficking and regulating transcription [1,2,22,23]. It is also known that the F-actin meshwork that forms in the nuclear space is essential for preventing chromosome loss and aneuploidy in the embryo [24]. Such aneuploidy is one of the main causes of death in cloned embryos [25]. "
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    ABSTRACT: Somatic cell nuclear transfer to an enucleated oocyte is used for reprogramming somatic cells with the aim of achieving totipotency, but most cloned embryos die in the uterus after transfer. While modifying epigenetic states of cloned embryos can improve their development, the production rate of cloned embryos can also be enhanced by changing other factors. It has already been shown that abnormal chromosome segregation (ACS) is a major cause of the developmental failure of cloned embryos and that Latrunculin A (LatA), an actin polymerization inhibitor, improves F-actin formation and birth rate of cloned embryos. Since F-actin is important for chromosome congression in embryos, here we examined the relation between ACS and F-actin in cloned embryos. Using LatA treatment, the occurrence of ACS decreased significantly whereas cloned embryo-specific epigenetic abnormalities such as dimethylation of histone H3 at lysine 9 (H3K9me2) could not be corrected. In contrast, when H3K9me2 was normalized using the G9a histone methyltransferase inhibitor BIX-01294, the Magea2 gene-essential for normal development but never before expressed in cloned embryos-was expressed. However, this did not increase the cloning success rate. Thus, non-epigenetic factors also play an important role in determining the efficiency of mouse cloning.
    PLoS ONE 10/2013; 8(10):e78380. DOI:10.1371/journal.pone.0078380 · 3.23 Impact Factor
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