title: CD98hc (SLC3A2) is a key regulator of keratinocyte adhesion.
abstract: BACKGROUND
  Adhesion of keratinocytes is crucial for maintaining the integrity of the skin, as demonstrated by the number of dermatological disorders of genetic origin that are associated with a defect of basal keratinocyte adhesion. Integrins are the main component of the molecular networks involved in this phenomenon, but there are many others. In a recent description of proteins associated to caveolae at the plasma membrane of human basal epidermal cells, we demonstrated that CD98hc is localized with β1 integrin.
  
  
  OBJECTIVE
  We investigated the CD98hc proteins interactions and the role of CD98hc in keratinocyte adhesion.
  
  
  METHODS
  CD98hc protein interaction was identified following co-immunoprecipitation and proteomic analysis using LTQ-FT mass spectrometer. Extinction of CD98hc gene expression using specific short hairpin RNA or over-expression of CD98hc lacking the β1 integrin binding site was used to evaluate the role of this protein in keratinocyte fate.
  
  
  RESULTS
  We show that CD98hc forms molecular complexes with β1 and β4 integrins in primary human keratinocytes and, using immunofluorescence, that these complexes are localized at the plasma membrane, in keeping with a role in adhesion. We confirmed that this protein is a key player of keratinocyte adhesion because in absence of interaction between CD98hc and integrins, β1 integrin failed to translocate from the cytoplasm to the plasma membrane and keratinocytes expressed epidermal differentiation markers.
  
  
  CONCLUSIONS
  All these data strongly suggested that CD98hc is involved in integrin trafficking and by consequence, in keratinocyte adhesion and differentiation.
authors.affiliation: CEA/iRCM/SCSR/LGRK, 2 rue G. Crémieux, Evry, France. glemaitre@istem.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Lemaître
authors.forename: Alexandre
authors.initials: A
authors.lastname: Stella
authors.forename: Jessica
authors.initials: J
authors.lastname: Feteira
authors.forename: Christine
authors.initials: C
authors.lastname: Baldeschi
authors.forename: Pierre
authors.initials: P
authors.lastname: Vaigot
authors.forename: Michèle T
authors.initials: MT
authors.lastname: Martin
authors.forename: Bernard
authors.initials: B
authors.lastname: Monsarrat
authors.forename: Gilles
authors.initials: G
authors.lastname: Waksman
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D039663:Integrin beta4 / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*
chemical_list: D027282:Fusion Regulatory Protein 1, Heavy Chain; D019012:Integrin beta1; D039663:Integrin beta4; C545989:SLC3A2 protein, human