The "Caveolae Brake Hypothesis" and the epidermal barrier

Truus Roelandt, C. Giddelo, G Denecker, M. Hupe, D. Crumrine, C. Heughebaert, A. Kusuma, M. Haftek, Diane Roseeuw, W. Declercq, K. Feingold, P.m. Elias, Jean-Pierre Hachem

Onderzoeksoutput: Meeting abstract (Journal)

Samenvatting

Epidermal permeability barrier is partly regulated by the polarized secretion of lamellar bodies (LB)
and their fusion with the apical plasma membrane of a terminally differentiated keratinocytes at
the stratum granulosum (SG)- stratum corneum (SC) junction. LB secretion creates cholesterol/glycosphingolipids
rich membrane domains resembling in composition lipid rafts (LR)/caveolae. We
found that the size of those domains is comparable to LR and that barrier stress modifies their
dynamics and morphology. To address the function of those domains, methyl-β-cyclodextrin (MβCD)-
topically treated hairless mice and/or caveolin-1 knockout mice (cav-1 -/-) were studied. MβCD
delayed barrier recovery following abrogation attributable to a decreased LB secretion, whereas
accelerated recovery in cav-1 -/- correlates with hyper-secretion and large raft domains formation
at the SG-SC interface. Following barrier abrogation cav-1 was found to translocate from the cytoplasmic
to raft domains, a key phenomenon for signaling terminal differentiation of keratinocytes.
The later could be inhibited by either monensin, an inhibitor of LB secretion and consequently
cav-1 translocation, and absence of cav-1. Caveolae proteins are delivered by LB trafficking and
serve as a “brake” for LR formation, LB secretion arrest and terminal differentiation. Finally, persistence
of rafts in cav-1 -/- increases epidermal propensity to hyperplasia. Similarly hyperproliferative
psoriatic epidermis is characterized by increased LR formation.
Originele taal-2English
Artikelnummer553
Pagina's (van-tot)S93-S93
Aantal pagina's1
TijdschriftJ Invest Dermatol
Volume128
Nummer van het tijdschriftS1
StatusPublished - apr 2008

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