title: Actin dynamics regulate immediate PAR-2-dependent responses to acute epidermal permeability barrier abrogation.
abstract: BACKGROUND
  Lamellar body (LB) secretion and terminal differentiation of stratum granulosum (SG) cells are signaled by both protease activated receptor-2 (PAR-2) and caveolin-1 (cav-1).
  
  
  OBJECTIVE
  To address the early dynamics of LB secretion, we examined cytoskeletal remodeling of keratinocytes in 3 mouse models following acute barrier abrogation: hairless mice, PAR-2 knockout (-/-) and cav-1 -/-.
  
  
  RESULTS
  Under basal conditions, globular (G)-actin accumulates in SG cells cytosol, while filamentous (F)-actin is restricted to peri-membrane domains. Barrier abrogation induces the apical movement of F-actin and the retreat of the SG-G-actin front, paralleled by upstream cytoskeletal kinases activation. This phenomenon was both enhanced by PAR-2 agonist, and inhibited by cytochalasin-D and in PAR-2 knockout mice. We found that plasma membrane conformational changes causing LB secretion are controlled by PAR-2-dependent cytoskeletal rearrangements. We next addressed the interaction dynamics between cytoskeleton and plasma membrane following PAR-2-induced actin stress fiber formation in both cav-1 -/- and wildtype cells. Actin stress fiber formation is increased in cav-1 -/- cells prior to and following PAR-2 agonist peptide-treatment, while absence of cav-1 inhibits E-cadherin-mediated cell-to-cell adhesion.
  
  
  CONCLUSIONS
  PAR-2 drives cytoskeletal/plasma membrane dynamics that regulate early LB secretion following barrier abrogation, stress fiber formation and keratinocyte adhesion.
authors.affiliation: Department of Dermatology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Truus
authors.initials: T
authors.lastname: Roelandt
authors.forename: Carol
authors.initials: C
authors.lastname: Heughebaert
authors.forename: Gunther
authors.initials: G
authors.lastname: Verween
authors.forename: Christina
authors.initials: C
authors.lastname: Giddelo
authors.forename: Gilbert
authors.initials: G
authors.lastname: Verbeken
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pirnay
authors.forename: Daniel
authors.initials: D
authors.lastname: Devos
authors.forename: Debra
authors.initials: D
authors.lastname: Crumrine
authors.forename: Diane
authors.initials: D
authors.lastname: Roseeuw
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hachem
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D003599:Cytoskeleton / Q000648:ultrastructure; D004817:Epidermis / Q000378:metabolism* / Q000648:ultrastructure; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D018345:Mice, Knockout; D010539:Permeability; D044464:Receptor, PAR-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D022502:Stress Fibers / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D051242:Caveolin 1; D044464:Receptor, PAR-2