Document Detail

The "caveolae brake hypothesis" and the epidermal barrier.
MedLine Citation:
PMID:  19005485     Owner:  NLM     Status:  MEDLINE    
Epidermal permeability barrier formation depends upon lamellar body (LB) secretion/fusion with the apical plasma membrane (APM) of outermost stratum granulosum (SG) cell, creating cholesterol/glycosphingolipid-enriched lipid rafts-like domains. We found that the dimensions of these domains are comparable to lipid raft in other cell types; and that acute barrier disruption regulates their size and dynamics. To assess the function of these LB-derived raft-like domains, we assessed APM dynamics and barrier recovery in methyl-beta-cyclodextrin (MbetaCD)-treated hairless mice and caveolin-1 knockouts (cav-1(-/-)). MbetaCD treatment impaired APM raft-like domain formation and barrier recovery. Accelerated barrier recovery is observed in cav-1(-/-) in parallel with expansion of raft-like domains. Barrier abrogation of normal epidermis resulted in translocation of cav-1 from the cytoplasm to raft-like membrane domains, restricting further raft-like domain formation and initiating terminal differentiation. Inhibition of LB secretion by monensin and absence of cav-1 delayed terminal differentiation. Furthermore, cav-1(-/-) mice exhibited an increased propensity to develop experimentally induced epidermal hyperplasia correlating with lipid raft persistence. Finally, the epidermal hyperplasia in psoriasis and Netherton syndrome is paralleled by increased lipid raft formation. These studies demonstrate that cav-1 delivery to the APM by LB trafficking to APM "brakes" further LB secretion, signals terminal differentiation, and regulates epidermal hyperproliferation.
Truus Roelandt; Christina Giddelo; Carol Heughebaert; Geertrui Denecker; Melanie Hupe; Debra Crumrine; Andy Kusuma; Marek Haftek; Diane Roseeuw; Wim Declercq; Kenneth R Feingold; Peter M Elias; Jean-Pierre Hachem
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-13
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  129     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-26     Completed Date:  2009-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  927-36     Citation Subset:  IM    
Department of Dermatology, Free University of Brussels, Brussels, Belgium.
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MeSH Terms
Caveolae / physiology*
Caveolin 1 / physiology
Epidermis / metabolism*,  pathology,  ultrastructure
Membrane Microdomains / physiology
Mice, Hairless
beta-Cyclodextrins / pharmacology
Reg. No./Substance:
0/Caveolin 1; 0/beta-Cyclodextrins; 0/methyl-beta-cyclodextrin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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