Microtubule-binding myosin required for nuclear anchoring and spindle assembly

Department of Zoology, University of Wisconsin, Madison, Madison, Wisconsin 53706, USA.
Nature (Impact Factor: 41.46). 10/2004; 431(7006):325-9. DOI: 10.1038/nature02834
Source: PubMed


Proper spindle positioning and orientation are essential for asymmetric cell division and require microtubule-actin filament (F-actin) interactions in many systems. Such interactions are particularly important in meiosis, where they mediate nuclear anchoring, as well as meiotic spindle assembly and rotation, two processes required for asymmetric cell division. Myosin-10 proteins are phosphoinositide-binding, actin-based motors that contain carboxy-terminal MyTH4 and FERM domains of unknown function. Here we show that Xenopus laevis myosin-10 (Myo10) associates with microtubules in vitro and in vivo, and is concentrated at the point where the meiotic spindle contacts the F-actin-rich cortex. Microtubule association is mediated by the MyTH4-FERM domains, which bind directly to purified microtubules. Disruption of Myo10 function disrupts nuclear anchoring, spindle assembly and spindle-F-actin association. Thus, this myosin has a novel and critically important role during meiosis in integrating the F-actin and microtubule cytoskeletons.

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Available from: Anna Sokac, Sep 30, 2015
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    • "in cytoskeleton , MTs and their regulated interplay are required for successful chromosome segregation ( Rodriguez et al . , 2003 ; Woolner et al . , 2008 ) . Recent studies demonstrated that myosin - 10 is an essential integrator of spindle MTs with cortical F - actin required for nuclear anchoring and spindle assembly in Xenopus laevis oocytes ( Weber et al . , 2004 ) . Other examples include the association of nonmuscle myosin - 2 ( MHC - A ) with MTs of the spindle apparatus ( Kelley et al . , 1996 ) and the localization of myosin - 5 at the MT organizing center during melanocyte cell division ( Wu et al . , 1998 ) . Diffusive interactions of myosin - 5 with MTs are assumed to be required for eff"
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    • "Disruption of Factin in Xenopus embryos also leads to spindle mispositioning in the outer epithelial cells (Woolner et al., 2008). Unconventional myosin-X, which binds both to microtubules and actin (Hirano et al., 2011; Weber et al., 2004), is required for spindle orientation in cultured cells (Toyoshima and Nishida, 2007). Indeed, a study of epithelial cells of Xenopus embryos shows that myosin-X and F-actin both contribute to the anchoring of the spindle at the cortex (Woolner et al., 2008). "
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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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    • "In fact, in our species, the cortex is the domain where GVBD preferentially occurs, a circumstance that probably rules out the necessity of a peripheral displacement of the newly formed MI spindle (Coticchio et al., 2011). However, it is tempting to speculate that the actin cluster may be involved in the anchoring of the spindle to the cortex (Weber et al., 2004) or in the control of the shape of spindle poles (Coticchio et al., 2013). Future studies will need to establish whether this actin-based formation is a constitutive element of the oocyte cytoskeleton or occurs only under specific conditions, as suggested by the rarity of its detection in our sample set. "
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    ABSTRACT: In mature mammalian oocytes, cortical f-actin distribution is polarized, as evidenced by a prominent cap subtended by the metaphase II (MII) spindle. Formation of a polarized actin cap is a consequence of a complex actomyosin-driven contractile process that directs polar body extrusion. Human mature oocytes also display a network of sub-oolemmal actin, but so far there has been no suggestion of an actin-rich domain in the vicinity of the spindle.By high-resolution confocal microscopy, we generated semi-quantitative data of the actin cytoskeleton in human mature and immature oocytes, with the aim to better understand the characteristics and remodelling of this cytoskeletal component in the female gamete. In mature MII oocytes, the cortical domain near the spindle showed a more intense actin signal in comparison to the opposite cortical domain (177.2±59.0 vs. 126.8±61.0, P<0.0001; data expressed in arbitrary units). The extent of cortical f-actin polarity was comparable between in vivo and in vitro matured oocytes. However, both the degree of polarity and relative abundance of signal were diminished with increasing maternal age. Mean intensity of cytoplasmic actin was significantly higher in oocytes matured in vitro derived from in vitro maturation (IVM) cycle, in comparison to oocytes matured in vivo or in vitro obtained from controlled ovarian stimulation cycles (35.0±8.0, 21.1±12.4 and 25.9±8.6, respectively; P=0.025). In germinal vesicle (GV)-stage oocytes obtained from both IVM and controlled ovarian stimulation cycles, cortical actin did not appear polarized, irrespective of whether the GV was located centrally or asymmetrically.These data indicate that, during maturation, cortical actin acquires a polarized distribution involving an accumulation in the domain adjacent the spindle. They also propose new questions concerning the existence of cytoplasmic actin in mature oocytes. Finally, they are suggestive of an influence of maternal age on the actin cytoskeleton.
    Molecular Human Reproduction 11/2013; 20(3). DOI:10.1093/molehr/gat085 · 3.75 Impact Factor
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