Regulated cleavage of a contact-mediated axon repellent.
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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Axons, Cell Adhesion, Cell Communication, Cell Membrane, Cells, Cultured, Disintegrins, Drosophila Proteins, Ephrin-A2, Gene Expression, Glycosylphosphatidylinositols, Growth Cones, Humans, Ligands, Metalloendopeptidases, Mice, Molecular Sequence Data, Mutation, Nervous System, Receptor Protein-Tyrosine Kinases, Receptor, EphA3, Recombinant Fusion Proteins, Signal Transduction, Transcription Factors, Tumor Cells, Cultured
Amino Acid Motifs, Amino Acid Sequence, Animals, Axons, Cell Adhesion, Cell Communication, Cell Membrane, Cells, Cultured, Disintegrins, Drosophila Proteins, Ephrin-A2, Gene Expression, Glycosylphosphatidylinositols, Growth Cones, Humans, Ligands, Metalloendopeptidases, Mice, Molecular Sequence Data, Mutation, Nervous System, Receptor Protein-Tyrosine Kinases, Receptor, EphA3, Recombinant Fusion Proteins, Signal Transduction, Transcription Factors, Tumor Cells, Cultured
Science
Date: Aug. 25, 2000
PubMed ID: 10958785
View in: Pubmed Google Scholar
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