Identification of a Novel Domain at the N Terminus of Caveolin-1 That Controls Rear Polarization of the Protein and Caveolae Formation

Details

• Personal Author:
  Beardsley AR ; Castranova, Vincent ; Flynn DC ; Liu J ; Millecchia LL ; Sun XH
• Description:
  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 ((TKEIDLVNRD55)-T-46) 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. [Description provided by NIOSH]
• Subjects:
  Chemistry Genetics Occupational Health Safety
• Keywords:
  Cell-biology Cell-function Cell-transformation Cellular-structures Chemical-reactions Chemical-synthesis Chemoreceptors Gene-mutation Genes Genetic-disorders Genetic-factors Genotoxic-effects Genotoxicity

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• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  282
• Issue:
  10
• NIOSHTIC Number:
  nn:20031872
• Citation:
  J Biol Chem 2007 Mar; 282(10):7232-7241
• Contact Point Address:
  Jun Liu, West Virginia University Health Science Center, Dept. of Physiology and Pharmacology, P.O. Box 9229, Morgantown, WV 26506-9229
• Email:
  junliu@hsc.wvu.edu
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:77533d10aeaeda0aa6e675e905377c691b8ff9e492ee3cb502e9c9fc1c54127ae6a559119f5bd1d8ec41416118297f9a8447e9ee285618494e800ee6b981cc48
• Download URL:
  https://stacks.cdc.gov/view/cdc/185992/cdc_185992_DS1.pdf
• File Type:
  [PDF - 841.57 KB ]