TRP Channel Regulates EGFR Signaling in Hair Morphogenesis and Skin Barrier Formation

SummaryA 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.

Graphical AbstractFigure optionsDownload high-quality image (503 K)Download as PowerPoint slideHighlights
► Mice deficient in TRPV3, EGFR, or TGF-α exhibit wavy hair coat and curly whiskers
► Activation of EGFR leads to increased TRPV3 channel activity in keratinocytes
► Activation of TRPV3 channel stimulates TGF-α release in keratinocytes
► TRPV3 regulates transglutaminase activity and skin barrier formation