Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion
- Alice Davy,
- Nicholas W. Gale,
- Elizabeth W. Murray,
- Richard A. Klinghoffer,
- Philippe Soriano,
- Claude Feuerstein, and
- Stephen M. Robbins
- Departments of Oncology and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N-4N1 Canada; Laboratorie de Physiologie Section Neurophysiologie, University Joseph Fourier, Pav Neurology, Institut National de la Santé et de la Recherche Médicale (INSERM) U318, Centre Hospitalier Universitaire de Grenoble, BP217, F-38043 Grenoble CEDEX 9, France; Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591 USA; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024 USA
Abstract
Eph receptor tyrosine kinases and their corresponding surface-bound ligands, the ephrins, provide cues to the migration of cells and growth cones during embryonic development. Here we show that ephrin-A5, which is attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidylinositol-anchor, induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate Eph receptor. The physiological response induced by this signaling event is concomitant with a change in the cellular architecture and adhesion of the ephrin-A5-expressing cells and requires the activity of the Fyn protein tyrosine kinase. This study stresses the relevance of bidirectional signaling involving the ephrins and Eph receptors during brain development.
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Footnotes
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↵Corresponding author.
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E-MAIL srobbins{at}ucalgary.ca; FAX 403-283-8727.
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- Received August 17, 1999.
- Accepted October 13, 1999.
- Cold Spring Harbor Laboratory Press
