TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation

Xiping Cheng, Jie Jin, Lily Hu, Dongbiao Shen, Xian ping Dong, Mohammad A. Samie, Jayne Knoff, Brian Eisinger, Mei Ling Liu, Susan M. Huang, Michael Caterina, Peter Dempsey, Lowell Evan Michael, Andrzej A. Dlugosz, Nancy C. Andrews, David E. Clapham, Haoxing Xu

Research output: Contribution to journalArticle

Abstract

A plethora of growth factors regulate keratinocyte proliferation and differentiation that control hair morphogenesis and skin barrier formation. Wavy hair phenotypes in mice result from naturally occurring loss-of-function mutations in the genes for TGF-α and EGFR. Conversely, excessive activities of TGF-α/EGFR result in hairless phenotypes and skin cancers. Unexpectedly, we found that mice lacking the Trpv3 gene also exhibit wavy hair coat and curly whiskers. Here we show that keratinocyte TRPV3, a member of the transient receptor potential (TRP) family of Ca2+-permeant channels, forms a signaling complex with TGF-α/EGFR. Activation of EGFR leads to increased TRPV3 channel activity, which in turn stimulates TGF-α release. TRPV3 is also required for the formation of the skin barrier by regulating the activities of transglutaminases, a family of Ca2+-dependent crosslinking enzymes essential for keratinocyte cornification. Our results show that a TRP channel plays a role in regulating growth factor signaling by direct complex formation.

Original languageEnglish (US)
Pages (from-to)331-343
Number of pages13
JournalCell
Volume141
Issue number2
DOIs
StatePublished - Apr 2010

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Keywords

  • Devbio
  • Signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cheng, X., Jin, J., Hu, L., Shen, D., Dong, X. P., Samie, M. A., Knoff, J., Eisinger, B., Liu, M. L., Huang, S. M., Caterina, M., Dempsey, P., Michael, L. E., Dlugosz, A. A., Andrews, N. C., Clapham, D. E., & Xu, H. (2010). TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation. Cell, 141(2), 331-343. https://doi.org/10.1016/j.cell.2010.03.013