The Drosophila Myosin VI Jaguar Is Required for Basal Protein Targeting and Correct Spindle Orientation in Mitotic Neuroblasts
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.
- SourceAvailable from: onlinelibrary.wiley.com[Show abstract] [Hide abstract]
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; DOI:10.1002/cm.21150 · 3.01 Impact Factor
- [Show abstract] [Hide abstract]
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
- [Show abstract] [Hide abstract]
ABSTRACT: The spindle directs chromosome partitioning in eukaryotes and, for the last three decades, has been considered primarily a structure based on microtubules, microtubule motors, and other microtubule binding proteins. However, a surprisingly large body of both old and new studies suggests roles for actin filaments (F-actin) and myosins (F-actin-based motor proteins) in spindle assembly and function. Here we review these data and conclude that in several cases the evidence for the participation of F-actin and myosins in spindle function is very strong, and in the situations where it is less strong, there is nevertheless enough evidence to warrant further investigation.Developmental Cell 09/2011; 21(3):410-9. DOI:10.1016/j.devcel.2011.07.018 · 10.37 Impact Factor