Distinct membrane compartmentalization and signaling of ephrin-A5 and ephrin-B1.
Eph receptor tyrosine kinases and their membrane-bound ligand ephrins form an essential cell communication system. Both ephrin classes have been shown to localize within cell surface lipid rafts, yet regulate different biological processes. In order to provide insight into this distinct behavior, we examined ephrin-A5 and B1 localization and signaling in murine fibroblasts and tissues. Results indicated that ephrin-A5 was constitutively present in detergent-resistant membrane fractions, while ephrin-B1 displayed translocation to membrane fractions upon stimulation. Ephrin-A5 and B1 were present in detergent-resistant membrane fractions with different buoyancies in vitro and in different raft fractions in vivo. Moreover, ephrin-A5 and B1 differentially influenced actin reorganization. Finally, microarray analysis revealed unique patterns of gene expression between the two ephrin classes. We thus demonstrate that distinct localization and compartmentalization provide insight into the subcellular basis for differential signaling observed in ephrin-A and B classes.
Campbell
Tessa N
TN
Departments of Oncology and Biochemistry & Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, HRIC 2AA22, 3330 Hospital Drive NW, Calgary, Alta., Canada T2N 4N1.
Davy
Alice
A
Liu
Yiping
Y
Arcellana-Panlilio
Mayi
M
Robbins
Stephen M
SM
D000818:Animals; D003599:Cytoskeleton / Q000648:ultrastructure; D036386:Ephrin-A5 / Q000032:analysis / Q000145:classification / Q000378:metabolism*; D036387:Ephrin-B1 / Q000032:analysis / Q000145:classification / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D041681:NIH 3T3 Cells
D036386:Ephrin-A5; D036387:Ephrin-B1