Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion.
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.
Davy
A
A
Departments of Oncology and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N-4N1 Canada.
Gale
N W
NW
Murray
E W
EW
Klinghoffer
R A
RA
Soriano
P
P
Feuerstein
C
C
Robbins
S M
SM
D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002451:Cell Compartmentation; D002460:Cell Line; D002540:Cerebral Cortex / Q000737:chemistry / Q000196:embryology / Q000473:pathology; D003599:Cytoskeleton / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036386:Ephrin-A5; D017261:Glycosylphosphatidylinositols / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
D004791:Enzyme Inhibitors; D036386:Ephrin-A5; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases