Regulated cleavage of a contact-mediated axon repellent

M. Hattori, M. Osterfield, J. G. Flanagan

Research output: Contribution to journalArticle

443 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1360-1365
Number of pages6
JournalScience
Volume289
Issue number5483
DOIs
StatePublished - Aug 25 2000
Externally publishedYes

ASJC Scopus subject areas

  • General

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