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Regulated Cleavage of a Contact-Mediated Axon Repellent
Open accessAbstract
Contact-mediated axon repulsion by ephrins raises an unresolved question: these cell surface ligands form a high-affinity multivalent complex with their receptors present on axons, yet rather than being bound, axons can be rapidly repelled. We show here that ephrin-A2 forms a stable complex with the metalloprotease Kuzbanian, involving interactions outside the cleavage region and the protease domain. Eph receptor binding triggered ephrin-A2 cleavage in a localized reaction specific to the cognate ligand. A cleavage-inhibiting mutation in ephrin-A2 delayed axon withdrawal. These studies reveal mechanisms for protease recognition and control of cell surface proteins, and, for ephrin-A2, they may provide a means for efficient axon detachment and termination of signaling.
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Cited by
EDWARDS, D., HANDSLEY, M., & PENNINGTON, C. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.001 · Cited by 1,161
Eph receptor signalling casts a wide net on cell behaviour
Pasquale, E. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1662 · Cited by 1,017
Huber, A. B., Kolodkin, A. L., Ginty, D. D., & Cloutier, J.-F. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.010302.081139 · Cited by 719
Postina, R., Schroeder, A., Dewachter, I., Bohl, J., Schmitt, U., Kojro, E., Prinzen, C., Endres, K., Hiemke, C., Blessing, M., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20864 · Cited by 638
Metalloproteinases: Mediators of Pathology and Regeneration in the CNS
Yong, V. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1807 · Cited by 582
Metadata
- Authors
- Hattori, M., Osterfield, M., & Flanagan, J. G.
- Venue
- Science
- Published
- 2000-08-25
- Volume
- 289
- Issue
- 5483
- Pages
- 1360-1365
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2081656219
- Cited by
- 518
- References
- 0
- FWCI
- 13.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Hattori, M., Osterfield, M., & Flanagan, J. G. (2000). Regulated Cleavage of a Contact-Mediated Axon Repellent. Science. https://doi.org/10.1126/science.289.5483.1360
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
