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© The Rockefeller University Press, 0021-9525/2000//263 $5.00
The Journal of Cell Biology, Volume 149, Number 2, , 2000 263-270

Ephrin-A5 Induces Collapse of Growth Cones by Activating Rho and Rho Kinase

^a Max-Planck-Institut für Entwicklungsbiologie, Abteilung I (Physikalische Biologie), D-72076 Tübingen, Germany
^b Institut für Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
^c DeveloGen AG, D-37079 Göttingen, Germany
Max-Planck-Institut für Entwicklungsbiologie, Abteilung (Physikalische Biologie), Spemannstrasse 35/1, D-72076 Tübingen, Germany.49-7071-601-30549-7071-601-341

bernhard.mueller{at}tuebingen.mpg.de

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.

Key Words: retinotectal • repulsive • Eph receptor • axon guidance • collapse assay

© 2000 The Rockefeller University Press

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• Jurney, W. M., Gallo, G., Letourneau, P. C., McLoon, S. C. (2002). Rac1-Mediated Endocytosis during Ephrin-A2- and Semaphorin 3A-Induced Growth Cone Collapse. J. Neurosci. 22: 6019-6028 [Abstract] [Full Text]  
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• Schmidt, A., Hall, A. (2002). Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 16: 1587-1609 [Full Text]  
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• Hall, C., Michael, G. J., Cann, N., Ferrari, G., Teo, M., Jacobs, T., Monfries, C., Lim, L. (2001). {alpha}2-Chimaerin, a Cdc42/Rac1 Regulator, Is Selectively Expressed in the Rat Embryonic Nervous System and Is Involved in Neuritogenesis in N1E-115 Neuroblastoma Cells. J. Neurosci. 21: 5191-5202 [Abstract] [Full Text]  
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