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: 9.71). 03/2003; 4(2):273-81. DOI: 10.1016/S1534-5807(03)00020-0
Source: PubMed


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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    ABSTRACT: Crosstalk between the actin cytoskeleton and microtubules promotes symmetry break to polarize cells for division, shape changes and migration. These cellular events are crucial for forming tissues, and drive the metastasis of cancer cells. Rho GTPases mediate the formation of different types of F-actin that confer changes in cortical tension and contraction, and can also be regulated by microtubules. For example, central spindle microtubules of the mitotic spindle stimulate RhoA activity to form long, unbranched F-actin that is crosslinked by nonmuscle myosin to form the contractile ring in the equatorial plane of the cell. There is greater cortical tension in this area of the cell in comparison to the poles, where the formation of short, branched F-actin is favored. In migrating cells, growing microtubules that reach into the leading edge promote Rac activation and the formation of short, branched F-actin for lamellipodia formation. A common theme that is emerging in many fields is that feedback can also occur from the cortex to alter microtubule stability. In this manner cells can dynamically respond to intrinsic or extrinsic cues to ensure that their division plane is always coupled with the segregation of DNA and cell fate determinants, or that they migrate properly to form a tissue. © 2013 Wiley Periodicals, Inc.
    Cytoskeleton 10/2013; 71(1). DOI:10.1002/cm.21150 · 3.12 Impact Factor
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    • "The Baz/Par6/aPKC complex directs the basal distribution of the cell-fate determinant Numb, an evolutionary conserved protein primarily known for its ability to inhibit the Notch signaling pathway, and the adaptor protein Miranda (Mira). This process depends on an intact actin cytoskeleton [33] and two myosin motors, MyoII and MyoVI, which operate downstream of the apical complex [34]. "
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    ABSTRACT: Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through controlled asymmetric divisions and is necessary to generate cellular diversity during development and to maintain adult tissue homeostasis. Disruption of this balance may result in premature depletion of the stem/progenitor cell pool, or abnormal growth. In many tissues, including the brain, dysregulated asymmetric divisions are associated with cancer. Whether there is a causal relationship between asymmetric cell division defects and cancer initiation is as yet not known. Here, we review the cellular and molecular mechanisms that regulate asymmetric cell divisions in the neural lineage and discuss the potential connections between this regulatory machinery and cancer.
    Cellular and Molecular Life Sciences CMLS 06/2013; 71(4). DOI:10.1007/s00018-013-1386-1 · 5.81 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 · 2.09 Impact Factor
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