Identification of a novel domain at the N terminus of caveolin-1 that controls rear polarization of the protein and caveolae formation

Xinghui Sun, Daniel C. Flynn, Vincent Castranova, Lyndell L. Millecchia, Andrew R. Beardsley, Jun Liu

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 ( 46TKEIDLVNRD55) 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-β-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.

Original languageEnglish (US)
Pages (from-to)7232-7241
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number10
DOIs
StatePublished - Mar 2 2007

Fingerprint

Caveolin 1
Caveolae
Polarization
Proteins
Depolarization
Amino Acids
Null Lymphocytes
Sequence Deletion
Endothelial cells
Human Umbilical Vein Endothelial Cells
Cyclodextrins
Protein Transport
Chemotaxis
Fibroblasts
Alanine
Substitution reactions

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Identification of a novel domain at the N terminus of caveolin-1 that controls rear polarization of the protein and caveolae formation. / Sun, Xinghui; Flynn, Daniel C.; Castranova, Vincent; Millecchia, Lyndell L.; Beardsley, Andrew R.; Liu, Jun.

In: Journal of Biological Chemistry, Vol. 282, No. 10, 02.03.2007, p. 7232-7241.

Research output: Contribution to journalArticle

Sun, Xinghui ; Flynn, Daniel C. ; Castranova, Vincent ; Millecchia, Lyndell L. ; Beardsley, Andrew R. ; Liu, Jun. / Identification of a novel domain at the N terminus of caveolin-1 that controls rear polarization of the protein and caveolae formation. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 10. pp. 7232-7241.
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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 ( 46TKEIDLVNRD55) 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-β-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.",
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