Publication Date:
2000-08-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hattori, M -- Osterfield, M -- Flanagan, J G -- EY11559/EY/NEI NIH HHS/ -- HD29417/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 25;289(5483):1360-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Program in Neuroscience, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10958785" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Motifs
;
Amino Acid Sequence
;
Animals
;
Axons/*physiology
;
Cell Adhesion
;
Cell Communication
;
Cell Membrane/metabolism
;
Cells, Cultured
;
Disintegrins/genetics/*metabolism
;
*Drosophila Proteins
;
Ephrin-A2
;
Gene Expression
;
Glycosylphosphatidylinositols/metabolism
;
Growth Cones/physiology
;
Humans
;
Ligands
;
Metalloendopeptidases/genetics/*metabolism
;
Mice
;
Molecular Sequence Data
;
Mutation
;
Nervous System/embryology/enzymology
;
Receptor Protein-Tyrosine Kinases/metabolism
;
Receptor, EphA3
;
Recombinant Fusion Proteins/metabolism
;
Signal Transduction
;
Transcription Factors/chemistry/genetics/*metabolism
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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