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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
Brief Report |
Ephrin-A5 Induces Collapse of Growth Cones by Activating Rho and Rho Kinase
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
Abbreviations used in this paper: f-EA5, fc-ephrin-A5; GC, growth cone; GST, glutathione S-transferase; MLC, myosin light chain; RGC, retinal ganglion cell; RMLC, regulatory MLC; ROCK, Rho kinase.
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