NIOSHTIC-2 Publications Search
Migration-activated caveolin rear polarization is controlled by a specific domain at the N-terminus.
Sun-XH; Flynn-DC; Castranova-V; Beardsley-AR; Liu-J
97th AACR Annual Meeting, April 1-5, 2006, Washington D.C. Philadelphia, PA: American Association for Cancer Research, 2006 Apr; 47:LB-201
Angiogenic growth factor-induced endothelial cell migration is a key step towards tumor angiogenesis. When cells are migrating, caveolin-1, the principle protein component of caveolae, is excluded from the leading edge and polarized to the cell rear. The migration-stimulated caveolin rear translocation appears to play an important role in endothelial cell polarization and directional movement. In the present study, we generated a series of domain deletion mutants of caveolin-1 as GFP-fusion proteins and investigated domain or sequence that was required for caveolin-1 polarization in migrating cells. Our results show that wild-type caveolin-1, Cav1-178-GFP, was polarized to the cell rear in migrating caveolin-1 deficient mouse embryonic fibroblasts (MEFs). In contrast, deletion of aa 1-60 prevented the molecule from polarization and, in turn, some of the mutant were located at the leading edge, suggesting that aa 1-60 were essential for caveolin-1 polarization. Interestingly, deletion of aa 1-60 did not prevent caveolin-1 polarization in HUVECs as well as wild-type MEFs, suggesting that Cav61-178-GFP mutant might be interacting with endogenous caveolin-1 during polarization. Consistent with this, Cav61-178-GFP and Cav61-178-Flag were co-immunoprecipitated with endogenous caveolin-1. Furthermore, Cav61-178 was incorporated into light membrane domains and mediated caveolae formation. Our results indicate that aa 1-60 in caveolin-1 were essential for its polarization in migrating cells.
Growth-factors; Cell-growth; Cell-migration; Laboratory-animals; Animals; Animal-studies
Abstract; Conference/Symposia Proceedings
97th American Association for Cancer Research Annual Meeting, April 1-5, 2006, Washington D.C.