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


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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    Full-text · Article · Jan 2014 · Journal of Cell Science
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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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    • "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.
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