The Drosophila Myosin VI Jaguar Is Required for Basal Protein Targeting and Correct Spindle Orientation in Mitotic Neuroblasts

Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Developmental Cell (Impact Factor: 10.37). 03/2003; 4(2):273-81. DOI: 10.1016/S1534-5807(03)00020-0
Source: PubMed

ABSTRACT Asymmetric cell divisions generate cellular diversity. In Drosophila, embryonic neuroblasts target cell fate determinants basally, rotate their spindles by 90 degrees to align with the apical-basal axis, and divide asymmetrically in a stem cell-like fashion. In this process, apically localized Bazooka recruits Inscuteable and other proteins to form an apical complex, which then specifies spindle orientation and basal localization of the cell fate determinants and their adapter proteins such as Miranda. Here we report that Miranda localization requires the unconventional myosin VI Jaguar (Jar). In jar null mutant embryos, Miranda is delocalized and the spindle is misoriented, but the Inscuteable crescent remains apical. Miranda directly binds to Jar, raising the possibility that Miranda and its associated proteins are translocated basally by this actin-based motor. Our studies demonstrate that a class VI myosin is necessary for basal protein targeting and spindle orientation in neuroblasts.

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    • "For example, Rho kinase inhibition downregulates nonmuscle myosin activity and disrupts the basal localization of Mira, Pros, and Numb [Barros et al., 2003]. Furthermore, Mira may bind to the myosin motor protein myosin VI (Jaguar), which could mediate its transport to the cortex [Petritsch et al., 2003]. As the cell cycle progresses and the mitotic spindle forms, additional complexes form at the apical side of the cell that tether microtubules to the apical pole (Fig. 2). "
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    Cytoskeleton 10/2013; 71. DOI:10.1002/cm.21150 · 3.01 Impact Factor
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    • "We have also observed that depletion of MVI affected PC12 cell proliferation. MVI involvement in the regulation of cell division was reported for the first time by Petritsch et al. (2003) who demonstrated that in Drosophila neuroblasts MVI isoform, Jaguar, was necessary for basal protein targeting and spindle orientation. Arden et al. (2007) have shown that in dividing epithelial MDCK cells localization of MVI changed dramatically and inhibition of its expression by siRNA led to a delay in metaphase progression and a cytokinesis defect. "
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    ABSTRACT: Myosin VI (MVI) is the only known myosin walking towards minus end of actin filaments and is believed to play distinct role(s) than other myosins. We addressed a role of this unique motor in secretory PC12 cells, derived from rat adrenal medulla pheochromocytoma using cell lines with reduced MVI synthesis (produced by means of siRNA). Decrease of MVI expression caused severe changes in cell size and morphology, and profound defects in actin cytoskeleton organization and Golgi structure. Also, significant inhibition of cell migration as well as cell proliferation was observed. Flow cytometric analysis revealed that MVI-deficient cells were arrested in G0/G1 phase of the cell cycle but did not undergo increased senescence as compared with control cells. Also, neither polyploidy nor aneuploidy were detected. Surprisingly, no significant effect on noradrenaline secretion was observed. These data indicate that in PC12 cells MVI is involved in cell migration and proliferation but is not crucial for stimulation-dependent catecholamine release.
    Journal of Muscle Research and Cell Motility 11/2011; 32(4-5):291-302. DOI:10.1007/s10974-011-9279-0 · 1.93 Impact Factor
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    • "However, whether this clustering is based on the kind of cortical flow described in Rosenblatt et al. (2004) is unknown and it may instead reflect forces exerted through retraction fibers or other cortical, F-actin-based structures (Kwon et al., 2008). Myosin-6 controls mitotic spindle rotation in Drosophila neuroblasts, and while the means by which this occurs are uncertain, Myosin-6 undergoes a redistribution during spindle rotation, suggestive of an active role (Petritsch et al., 2003). Dachs, an atypical myosin, controls spindle orientation in developing Drosophila wing epithelia by a completely different mechanism. "
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