Negative guidance factor-induced macropinocytosis in the growth cone plays a critical role in repulsive axon turning
Authors
Kolpak, Adrianne L.Jiang, Jun
Guo, Daorong
Standley, Clive
Bellve, Karl D.
Fogarty, Kevin E.
Bao, Zheng-Zheng
UMass Chan Affiliations
Department of PhysiologyDepartment of Cell Biology
Department of Medicine, Division of Endocrinology and Metabolism
Document Type
Journal ArticlePublication Date
2009-08-28Keywords
AnimalsAxons
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
Metadata
Show full item recordAbstract
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.2355-09.2009Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39365PubMed ID
19710302Related Resources
ae974a485f413a2113503eed53cd6c53
10.1523/JNEUROSCI.2355-09.2009