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

doi:10.1083/jcb.149.2.263

This Article

	Full Text
	PDF (Full Text)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Wahl, S.
	Articles by Mueller, B. K.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Wahl, S.
	Articles by Mueller, B. K.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2000/4/263/ $5.00
The Journal of Cell Biology, Volume 149, Number 2, April 17, 2000 263-270

Brief Report

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

Siegfried Wahl^a, Holger Barth^b, Thomas Ciossek^c, Klaus Aktories^b, and Bernhard K. Mueller^a
^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

Correspondence to: Bernhard K. Mueller, Max-Planck-Institut für Entwicklungsbiologie, Abteilung (Physikalische Biologie), Spemannstrasse 35/1, D-72076 Tübingen, Germany. Tel:49-7071-601-341 Fax:49-7071-601-305 E-mail:bernhard.mueller{at}tuebingen.mpg.de.

The ephrins, ligands of Eph receptor tyrosine kinases, havebeen shown to act as repulsive guidance molecules and to inducecollapse of neuronal growth cones. For the first time, we showthat the ephrin-A5 collapse is mediated by activation of thesmall GTPase Rho and its downstream effector Rho kinase. Inephrin-A5–treated retinal ganglion cell cultures, Rhowas activated and Rac was downregulated. Pretreatment of ganglioncell axons with C3-transferase, a specific inhibitor of theRho GTPase, or with Y-27632, a specific inhibitor of the Rhokinase, strongly reduced the collapse rate of retinal growthcones. These results suggest that activation of Rho and itsdownstream effector Rho kinase are important elements of theephrin-A5 signal transduction pathway.

Key Words: retinotectal, repulsive, Eph receptor, axon guidance, collapseassay

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Strochlic, L., Dwivedy, A., van Horck, F. P. G., Falk, J., Holt, C. E. (2008). A role for S1P signalling in axon guidance in the Xenopus visual system. Development 135: 333-342 [Abstract] [Full Text]
Zhang, Y., Sawada, T., Jing, X., Yokote, H., Yan, X., Sakaguchi, K. (2007). Regulation of Ephexin1, a Guanine Nucleotide Exchange Factor of Rho Family GTPases, by Fibroblast Growth Factor Receptor-mediated Tyrosine Phosphorylation. J. Biol. Chem. 282: 31103-31112 [Abstract] [Full Text]
Parri, M., Buricchi, F., Giannoni, E., Grimaldi, G., Mello, T., Raugei, G., Ramponi, G., Chiarugi, P. (2007). EphrinA1 Activates a Src/Focal Adhesion Kinase-mediated Motility Response Leading to Rho-dependent Actino/Myosin Contractility. J. Biol. Chem. 282: 19619-19628 [Abstract] [Full Text]
Chen, J., Wu, J., Apostolova, I., Skup, M., Irintchev, A., Kugler, S., Schachner, M. (2007). Adeno-associated virus-mediated L1 expression promotes functional recovery after spinal cord injury. Brain 130: 954-969 [Abstract] [Full Text]
Evans, I. R., Renne, T., Gertler, F. B., Nobes, C. D. (2007). Ena/VASP proteins mediate repulsion from ephrin ligands. J. Cell Sci. 120: 289-298 [Abstract] [Full Text]
Murata, T., Ohnishi, H., Okazawa, H., Murata, Y., Kusakari, S., Hayashi, Y., Miyashita, M., Itoh, H., Oldenborg, P.-A., Furuya, N., Matozaki, T. (2006). CD47 Promotes Neuronal Development through Src- and FRG/Vav2-Mediated Activation of Rac and Cdc42. J. Neurosci. 26: 12397-12407 [Abstract] [Full Text]
Gallo, G. (2006). RhoA-kinase coordinates F-actin organization and myosin II activity during semaphorin-3A-induced axon retraction.. J. Cell Sci. 119: 3413-3423 [Abstract] [Full Text]
Rajnicek, A. M., Foubister, L. E., McCaig, C. D. (2006). Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field. J. Cell Sci. 119: 1723-1735 [Abstract] [Full Text]
Orioli, D., Colaluca, I. N., Stefanini, M., Riva, S., Dotti, C. G., Peverali, F. A. (2006). Rac3-induced Neuritogenesis Requires Binding to Neurabin I. Mol. Biol. Cell 17: 2391-2400 [Abstract] [Full Text]
Dail, M., Richter, M., Godement, P., Pasquale, E. B. (2006). Eph receptors inactivate R-Ras through different mechanisms to achieve cell repulsion. J. Cell Sci. 119: 1244-1254 [Abstract] [Full Text]
Nicol, X., Muzerelle, A., Rio, J. P., Metin, C., Gaspar, P. (2006). Requirement of Adenylate Cyclase 1 for the Ephrin-A5-Dependent Retraction of Exuberant Retinal Axons. J. Neurosci. 26: 862-872 [Abstract] [Full Text]
Arimura, N., Menager, C., Kawano, Y., Yoshimura, T., Kawabata, S., Hattori, A., Fukata, Y., Amano, M., Goshima, Y., Inagaki, M., Morone, N., Usukura, J., Kaibuchi, K. (2005). Phosphorylation by Rho Kinase Regulates CRMP-2 Activity in Growth Cones. Mol. Cell. Biol. 25: 9973-9984 [Abstract] [Full Text]
Marler, K. J. M., Kozma, R., Ahmed, S., Dong, J.-M., Hall, C., Lim, L. (2005). Outgrowth of Neurites from NIE-115 Neuroblastoma Cells Is Prevented on Repulsive Substrates through the Action of PAK. Mol. Cell. Biol. 25: 5226-5241 [Abstract] [Full Text]
Aasheim, H.-C., Delabie, J., Finne, E. F. (2005). Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2. Blood 105: 2869-2876 [Abstract] [Full Text]
Jin, M., Guan, C.-b., Jiang, Y.-a., Chen, G., Zhao, C.-t., Cui, K., Song, Y.-q., Wu, C.-p., Poo, M.-m., Yuan, X.-b. (2005). Ca2+-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth Cones. J. Neurosci. 25: 2338-2347 [Abstract] [Full Text]
Govek, E.-E., Newey, S. E., Van Aelst, L. (2005). The role of the Rho GTPases in neuronal development. Genes Dev. 19: 1-49 [Abstract] [Full Text]
Goldshmit, Y., Galea, M. P., Wise, G., Bartlett, P. F., Turnley, A. M. (2004). Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice. J. Neurosci. 24: 10064-10073 [Abstract] [Full Text]
Brown, M., Jacobs, T., Eickholt, B., Ferrari, G., Teo, M., Monfries, C., Qi, R. Z., Leung, T., Lim, L., Hall, C. (2004). {alpha}2-Chimaerin, Cyclin-Dependent Kinase 5/p35, and Its Target Collapsin Response Mediator Protein-2 Are Essential Components in Semaphorin 3A-Induced Growth-Cone Collapse. J. Neurosci. 24: 8994-9004 [Abstract] [Full Text]
Watanabe, H., Yokozeki, T., Yamazaki, M., Miyazaki, H., Sasaki, T., Maehama, T., Itoh, K., Frohman, M. A., Kanaho, Y. (2004). Essential Role for Phospholipase D2 Activation Downstream of ERK MAP Kinase in Nerve Growth Factor-stimulated Neurite Outgrowth from PC12 Cells. J. Biol. Chem. 279: 37870-37877 [Abstract] [Full Text]
Barth, H., Aktories, K., Popoff, M. R., Stiles, B. G. (2004). Binary Bacterial Toxins: Biochemistry, Biology, and Applications of Common Clostridium and Bacillus Proteins. Microbiol. Mol. Biol. Rev. 68: 373-402 [Abstract] [Full Text]
Turner, L. J., Nicholls, S., Hall, A. (2004). The Activity of the Plexin-A1 Receptor Is Regulated by Rac. J. Biol. Chem. 279: 33199-33205 [Abstract] [Full Text]
Miyashita, M., Ohnishi, H., Okazawa, H., Tomonaga, H., Hayashi, A., Fujimoto, T.-T., Furuya, N., Matozaki, T. (2004). Promotion of Neurite and Filopodium Formation by CD47: Roles of Integrins, Rac, and Cdc42. Mol. Biol. Cell 15: 3950-3963 [Abstract] [Full Text]
Aoki, M., Yamashita, T., Tohyama, M. (2004). EphA Receptors Direct the Differentiation of Mammalian Neural Precursor Cells through a Mitogen-activated Protein Kinase-dependent Pathway. J. Biol. Chem. 279: 32643-32650 [Abstract] [Full Text]
Knoll, B., Drescher, U. (2004). Src Family Kinases Are Involved in EphA Receptor-Mediated Retinal Axon Guidance. J. Neurosci. 24: 6248-6257 [Abstract] [Full Text]
Brantley-Sieders, D. M., Caughron, J., Hicks, D., Pozzi, A., Ruiz, J. C., Chen, J. (2004). EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J. Cell Sci. 117: 2037-2049 [Abstract] [Full Text]
Lai, K.-O., Chen, Y., Po, H.-M., Lok, K.-C., Gong, K., Ip, N. Y. (2004). Identification of the Jak/Stat Proteins as Novel Downstream Targets of EphA4 Signaling in Muscle: IMPLICATIONS IN THE REGULATION OF ACETYLCHOLINESTERASE EXPRESSION. J. Biol. Chem. 279: 13383-13392 [Abstract] [Full Text]
Leemhuis, J., Boutillier, S., Barth, H., Feuerstein, T. J., Brock, C., Nurnberg, B., Aktories, K., Meyer, D. K. (2004). Rho GTPases and Phosphoinositide 3-Kinase Organize Formation of Branched Dendrites. J. Biol. Chem. 279: 585-596 [Abstract] [Full Text]
SOMLYO, A. P., SOMLYO, A. V. (2003). Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase. Physiol. Rev. 83: 1325-1358 [Abstract] [Full Text]
Miao, H., Nickel, C. H., Cantley, L. G., Bruggeman, L. A., Bennardo, L. N., Wang, B. (2003). EphA kinase activation regulates HGF-induced epithelial branching morphogenesis. J. Cell Biol. 162: 1281-1292 [Abstract] [Full Text]
Dubreuil, C. I., Winton, M. J., McKerracher, L. (2003). Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J. Cell Biol. 162: 233-243 [Abstract] [Full Text]
Murai, K. K., Pasquale, E. B. (2003). `Eph'ective signaling: forward, reverse and crosstalk. J. Cell Sci. 116: 2823-2832 [Abstract] [Full Text]
Weinl, C., Drescher, U., Lang, S., Bonhoeffer, F., Loschinger, J. (2003). On the turning of Xenopus retinal axons induced by ephrin-A5. Development 130: 1635-1643 [Abstract] [Full Text]
Dontchev, V. D., Letourneau, P. C. (2003). Growth Cones Integrate Signaling from Multiple Guidance Cues. J. Histochem. Cytochem. 51: 435-444 [Abstract] [Full Text]
Endo, M., Ohashi, K., Sasaki, Y., Goshima, Y., Niwa, R., Uemura, T., Mizuno, K. (2003). Control of Growth Cone Motility and Morphology by LIM Kinase and Slingshot via Phosphorylation and Dephosphorylation of Cofilin. J. Neurosci. 23: 2527-2537 [Abstract] [Full Text]
Deroanne, C., Vouret-Craviari, V., Wang, B., Pouyssegur, J. (2003). EphrinA1 inactivates integrin-mediated vascular smooth muscle cell spreading via the Rac/PAK pathway. J. Cell Sci. 116: 1367-1376 [Abstract] [Full Text]
Sugimoto, N., Takuwa, N., Okamoto, H., Sakurada, S., Takuwa, Y. (2003). Inhibitory and Stimulatory Regulation of Rac and Cell Motility by the G12/13-Rho and Gi Pathways Integrated Downstream of a Single G Protein-Coupled Sphingosine-1-Phosphate Receptor Isoform. Mol. Cell. Biol. 23: 1534-1545 [Abstract] [Full Text]
Chalasani, S. H., Sabelko, K. A., Sunshine, M. J., Littman, D. R., Raper, J. A. (2003). A Chemokine, SDF-1, Reduces the Effectiveness of Multiple Axonal Repellents and Is Required for Normal Axon Pathfinding. J. Neurosci. 23: 1360-1371 [Abstract] [Full Text]
Fournier, A. E., Takizawa, B. T., Strittmatter, S. M. (2003). Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS. J. Neurosci. 23: 1416-1423 [Abstract] [Full Text]
Demyanenko, G. P., Maness, P. F. (2003). The L1 Cell Adhesion Molecule Is Essential for Topographic Mapping of Retinal Axons. J. Neurosci. 23: 530-538 [Abstract] [Full Text]
Niederost, B., Oertle, T., Fritsche, J., McKinney, R. A., Bandtlow, C. E. (2002). Nogo-A and Myelin-Associated Glycoprotein Mediate Neurite Growth Inhibition by Antagonistic Regulation of RhoA and Rac1. J. Neurosci. 22: 10368-10376 [Abstract] [Full Text]
Gallo, G., Yee, H. F. Jr., Letourneau, P. C. (2002). Actin turnover is required to prevent axon retraction driven by endogenous actomyosin contractility. J. Cell Biol. 158: 1219-1228 [Abstract] [Full Text]
Dergham, P., Ellezam, B., Essagian, C., Avedissian, H., Lubell, W. D., McKerracher, L. (2002). Rho Signaling Pathway Targeted to Promote Spinal Cord Repair. J. Neurosci. 22: 6570-6577 [Abstract] [Full Text]
Dontchev, V. D., Letourneau, P. C. (2002). Nerve Growth Factor and Semaphorin 3A Signaling Pathways Interact in Regulating Sensory Neuronal Growth Cone Motility. J. Neurosci. 22: 6659-6669 [Abstract] [Full Text]
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]
Prevost, N., Woulfe, D., Tanaka, T., Brass, L. F. (2002). Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred. Proc. Natl. Acad. Sci. USA 99: 9219-9224 [Abstract] [Full Text]
Kwon, B. K., Borisoff, J. F., Tetzlaff, W. (2002). Molecular Targets for Therapeutic Intervention after Spinal Cord Injury. Mol. Interv. 2: 244-258 [Abstract] [Full Text]
Schmidt, A., Hall, A. (2002). Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 16: 1587-1609 [Full Text]
Yamazaki, M., Miyazaki, H., Watanabe, H., Sasaki, T., Maehama, T., Frohman, M. A., Kanaho, Y. (2002). Phosphatidylinositol 4-Phosphate 5-Kinase Is Essential for ROCK-mediated Neurite Remodeling. J. Biol. Chem. 277: 17226-17230 [Abstract] [Full Text]
Li, X., Saint-Cyr-Proulx, E., Aktories, K., Lamarche-Vane, N. (2002). Rac1 and Cdc42 but Not RhoA or Rho Kinase Activities Are Required for Neurite Outgrowth Induced by the Netrin-1 Receptor DCC (Deleted in Colorectal Cancer) in N1E-115 Neuroblastoma Cells. J. Biol. Chem. 277: 15207-15214 [Abstract] [Full Text]
Kim, M. D., Kolodziej, P., Chiba, A. (2002). Growth Cone Pathfinding and Filopodial Dynamics Are Mediated Separately by Cdc42 Activation. J. Neurosci. 22: 1794-1806 [Abstract] [Full Text]
Zanata, S. M., Hovatta, I., Rohm, B., Puschel, A. W. (2002). Antagonistic Effects of Rnd1 and RhoD GTPases Regulate Receptor Activity in Semaphorin 3A-Induced Cytoskeletal Collapse. J. Neurosci. 22: 471-477 [Abstract] [Full Text]
Lawrenson, I. D., Wimmer-Kleikamp, S. H., Lock, P., Schoenwaelder, S. M., Down, M., Boyd, A. W., Alewood, P. F., Lackmann, M. (2002). Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J. Cell Sci. 115: 1059-1072 [Abstract] [Full Text]
Boyd, A. W., Lackmann, M. (2001). Signals from Eph and Ephrin Proteins: A Developmental Tool Kit. Sci Signal 2001: re20-re20 [Abstract] [Full Text]
Hall, C., Brown, M., Jacobs, T., Ferrari, G., Cann, N., Teo, M., Monfries, C., Lim, L. (2001). Collapsin Response Mediator Protein Switches RhoA and Rac1 Morphology in N1E-115 Neuroblastoma Cells and Is Regulated by Rho Kinase. J. Biol. Chem. 276: 43482-43486 [Abstract] [Full Text]
Stepanek, L., Sun, Q. L., Wang, J., Wang, C., Bixby, J. L. (2001). CRYP-2/cPTPRO is a neurite inhibitory repulsive guidance cue for retinal neurons in vitro. J. Cell Biol. 154: 867-878 [Abstract] [Full Text]
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]
Yamaguchi, Y., Katoh, H., Yasui, H., Mori, K., Negishi, M. (2001). RhoA Inhibits the Nerve Growth Factor-induced Rac1 Activation through Rho-associated Kinase-dependent Pathway. J. Biol. Chem. 276: 18977-18983 [Abstract] [Full Text]