Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase.
The ephrins, ligands of Eph receptor tyrosine kinases, have been shown to act as repulsive guidance molecules and to induce collapse of neuronal growth cones. For the first time, we show that the ephrin-A5 collapse is mediated by activation of the small GTPase Rho and its downstream effector Rho kinase. In ephrin-A5-treated retinal ganglion cell cultures, Rho was activated and Rac was downregulated. Pretreatment of ganglion cell axons with C3-transferase, a specific inhibitor of the Rho GTPase, or with Y-27632, a specific inhibitor of the Rho kinase, strongly reduced the collapse rate of retinal growth cones. These results suggest that activation of Rho and its downstream effector Rho kinase are important elements of the ephrin-A5 signal transduction pathway.
Wahl
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Max-Planck-Institut für Entwicklungsbiologie, Abteilung I (Physikalische Biologie), D-72076 Tübingen, Germany.
Barth
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Ciossek
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Aktories
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Mueller
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BK
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D001905:Botulinum Toxins; D002478:Cells, Cultured; D002642:Chick Embryo; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036386:Ephrin-A5; D005982:Glutathione Transferase / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000502:physiology*; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D036386:Ephrin-A5; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C108830:Y 27632; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins