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    Negative guidance factor-induced macropinocytosis in the growth cone plays a critical role in repulsive axon turning

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    Authors
    Kolpak, Adrianne L.
    Jiang, Jun
    Guo, Daorong
    Standley, Clive
    Bellve, Karl D.
    Fogarty, Kevin E.
    Bao, Zheng-Zheng
    UMass Chan Affiliations
    Department of Physiology
    Department of Cell Biology
    Department of Medicine, Division of Endocrinology and Metabolism
    Document Type
    Journal Article
    Publication Date
    2009-08-28
    Keywords
    Animals
    Axons
    Cells, Cultured
    Chick Embryo
    Dextrans
    Dose-Response Relationship, Drug
    Drug Interactions
    Enzyme Inhibitors
    Green Fluorescent Proteins
    Growth Cones
    Hedgehog Proteins
    Myosin Type II
    Pinocytosis
    Retinal Ganglion Cells
    Tetradecanoylphorbol Acetate
    Time Factors
    Transfection
    Transferrin
    Veratrum Alkaloids
    rho GTP-Binding Proteins
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748960/
    Abstract
    Macropinocytosis is a type of poorly characterized fluid-phase endocytosis that results in formation of relatively large vesicles. We report that Sonic hedgehog (Shh) protein induces macropinocytosis in the axons through activation of a noncanonical signaling pathway, including Rho GTPase and nonmuscle myosin II. Macropinocytosis induced by Shh is independent of clathrin-mediated endocytosis but dependent on dynamin, myosin II, and Rho GTPase activities. Inhibitors of macropinocytosis also abolished the negative effects of Shh on axonal growth, including growth cone collapse and chemorepulsive axon turning but not turning per se. Conversely, activation of myosin II or treatment of phorbol ester induces macropinocytosis in the axons and elicits growth cone collapse and repulsive axon turning. Furthermore, macropinocytosis is also induced by ephrin-A2, and inhibition of dynamin abolished repulsive axon turning induced by ephrin-A2. Macropinocytosis can be induced ex vivo by high Shh, correlating with axon retraction. These results demonstrate that macropinocytosis-mediated membrane trafficking is an important cellular mechanism involved in axon chemorepulsion induced by negative guidance factors.
    Source

    J Neurosci. 2009 Aug 26;29(34):10488-98. Link to article on publisher's site

    DOI
    10.1523/JNEUROSCI.2355-09.2009
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/39365
    PubMed ID
    19710302
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1523/JNEUROSCI.2355-09.2009
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