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[Fred_CALICO]

• ABSTRACT
  
  Skin aging is linked to reduced epidermal proliferation and general extracellular matrix atrophy. This involves factors such as the cell adhesion receptors integrins and amino acid transporters. CD98hc (SLC3A2), a heterodimeric amino acid transporter, modulates integrin signaling in vitro. We unravel CD98hc functions in vivo in skin. We report thatCD98hc invalidation has no appreciable effect on cell adhesion, clearly showing thatCD98hc disruption phenocopies neither CD98hc knockdown in cultured keratinocytes nor epidermal β1 integrin loss in vivo. Instead, we show that CD98hc deletion in murine epidermis results in improper skin homeostasis and epidermal wound healing. These defects resemble aged skin alterations and correlate with reduction of CD98hc expression observed in elderly mice. We also demonstrate that CD98hc absence in vivo induces defects as early as integrin-dependent Src activation. We decipher the molecular mechanisms involved in vivo by revealing a crucial role of the CD98hc/integrins/Rho guanine nucleotide exchange factor (GEF) leukemia-associated RhoGEF (LARG)/RhoA pathway in skin homeostasis. Finally, we demonstrate that the deregulation of RhoA activation in the absence of CD98hc is also a result of impaired CD98hc-dependent amino acid transports.
  
• Submitted: 24 July 2012
• Accepted: 7 December 2012

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Articles Citing This Article

• CD98hc (SLC3A2) regulation of skin homeostasis wanes with ageJCB 2013 200:i5
  
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• CORRESPONDENCE Chloé C. Féral: chloe.feral@inserm.fr

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Edited by sell58, 23 January 2013 - 04:39 PM.