title: Identification of a novel domain at the N terminus of caveolin-1 that controls rear polarization of the protein and caveolae formation.
abstract: When cells are migrating, caveolin-1, the principal protein component of caveolae, is excluded from the leading edge and polarized at the cell rear. The dynamic feature depends on a specific sequence motif that directs intracellular trafficking of the protein. Deletion mutation analysis revealed a putative polarization domain at the N terminus of caveolin-1, between amino acids 32-60. Alanine substitution identified a minimal sequence of 10 residues ((46)TKEIDLVNRD(55)) necessary for caveolin-1 rear polarization. Interestingly, deletion of amino acids 1-60 did not prevent the polarization of caveolin-1 in human umbilical vein endothelial cells or wild-type mouse embryonic fibroblasts because of an interaction of Cav(61-178) mutant with endogenous caveolin-1. Surprisingly, expression of the depolarization mutant in caveolin-1 null cells dramatically impeded caveolae formation. Furthermore, knockdown of caveolae formation by methyl-beta-cyclodextrin failed to prevent wild-type caveolin-1 rear polarization. Importantly, genetic depletion of caveolin-1 led to disoriented migration, which can be rescued by full-length caveolin-1 but not the depolarization mutant, indicating a role of caveolin-1 polarity in chemotaxis. Thus, we have identified a sequence motif that is essential for caveolin-1 rear polarization and caveolae formation.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia 26506, USA.
authors.forename: Xing-Hui
authors.initials: XH
authors.lastname: Sun
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Flynn
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Lyndell L
authors.initials: LL
authors.lastname: Millecchia
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Beardsley
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1 / Q000737:chemistry* / Q000502:physiology; D002465:Cell Movement; D002478:Cells, Cultured; D051379:Mice; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D051242:Caveolin 1