Abstract
The Frizzled receptor and Dishevelled effector regulate mitotic spindle orientation in both vertebrates and invertebrates, but how Dishevelled orients the mitotic spindle is unknown. Using the Drosophila S2 cell "induced polarity" system, we find that Dishevelled cortical polarity is sufficient to orient the spindle and that Dishevelled's DEP domain mediates this function. This domain binds a C-terminal domain of Mud (the Drosophila NuMA ortholog), and Mud is required for Dishevelled-mediated spindle orientation. In Drosophila, Frizzled-Dishevelled planar cell polarity (PCP) orients the sensory organ precursor (pI) spindle along the anterior-posterior axis. We show that Dishevelled and Mud colocalize at the posterior cortex of pI, Mud localization at the posterior cortex requires Dsh, and Mud loss-of-function randomizes spindle orientation. During zebrafish gastrulation, the Wnt11-Frizzled-Dishevelled PCP pathway orients spindles along the animal-vegetal axis, and reducing NuMA levels disrupts spindle orientation. Overall, we describe a Frizzled-Dishevelled-NuMA pathway that orients division from Drosophila to vertebrates.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Cell Cycle Proteins
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Cell Division / physiology*
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Cell Line
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Cell Lineage
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Cell Polarity / physiology*
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Dishevelled Proteins
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster* / cytology
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Drosophila melanogaster* / physiology
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Dyneins / metabolism
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Embryo, Nonmammalian / anatomy & histology
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Embryo, Nonmammalian / physiology
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Frizzled Receptors / genetics
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Frizzled Receptors / metabolism*
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Gastrulation
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Guanine Nucleotide Dissociation Inhibitors / genetics
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Guanine Nucleotide Dissociation Inhibitors / metabolism
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Humans
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nuclear Matrix-Associated Proteins / genetics
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Nuclear Matrix-Associated Proteins / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology
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Spindle Apparatus / metabolism
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
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Zebrafish* / anatomy & histology
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Zebrafish* / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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Dishevelled Proteins
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Drosophila Proteins
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Frizzled Receptors
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Guanine Nucleotide Dissociation Inhibitors
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Membrane Proteins
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Mud protein, Drosophila
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Nerve Tissue Proteins
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Nuclear Matrix-Associated Proteins
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Phosphoproteins
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Pins protein, Drosophila
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Recombinant Fusion Proteins
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Zebrafish Proteins
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dsh protein, Drosophila
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Dyneins