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 J. Caterina; Peter Dempsey; Lowell Evan Michael; Andrzej A. Dlugosz; Nancy C. Andrews; David E. Clapham; Haoxing Xu

doi:10.1016/j.cell.2010.03.013

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 J. Caterina, Peter Dempsey, Lowell Evan Michael, Andrzej A. Dlugosz, Nancy C. Andrews, David E. Clapham, Haoxing Xu

Research output: Contribution to journal › Article › peer-review

263 Citations (Scopus)

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 language	English
Pages (from-to)	331-343
Number of pages	13
Journal	Cell
Volume	141
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2010.03.013
Publication status	Published - Apr 2010
Externally published	Yes

Bibliographical note

Funding Information:
This work is supported by HHMI (to N.C.A and D.E.C), startup funds to H.X. from the Department of MCDB and Biological Science Scholar Program, and the University of Michigan and NIH RO1 grants (NS062792 to H.X. and AR045973 to A.A.D.). We thank Dr. Leonidas Tsiokas for the EGFR construct, Dr. Nan Hatch and Dr. Dave Ornitz for the FGFR2 constructs, and Dr. Makato Suzuki for TRPV4 KO mice. We are grateful to Y. Fujiwara (Division of Hematology Transgenic core facility), S. Hein, X. Wang (Rockefeller University), X. Wang, E. Mills, R. Hume, J. Kuwada, M. Akaaboune, and C. Collins for assistance and L. Yue and D. Ren for comments on an earlier version of the manuscript. We appreciate the encouragement and helpful comments from other members of the Xu and Clapham laboratories. D.E.C. is founder of Hydra, which is currently working on TRPV3 antagonists.

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2010.03.013

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. J., 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

@article{7493354278d74b078374cdf9120413d2,

title = "TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation",

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.",

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

note = "Funding Information: This work is supported by HHMI (to N.C.A and D.E.C), startup funds to H.X. from the Department of MCDB and Biological Science Scholar Program, and the University of Michigan and NIH RO1 grants (NS062792 to H.X. and AR045973 to A.A.D.). We thank Dr. Leonidas Tsiokas for the EGFR construct, Dr. Nan Hatch and Dr. Dave Ornitz for the FGFR2 constructs, and Dr. Makato Suzuki for TRPV4 KO mice. We are grateful to Y. Fujiwara (Division of Hematology Transgenic core facility), S. Hein, X. Wang (Rockefeller University), X. Wang, E. Mills, R. Hume, J. Kuwada, M. Akaaboune, and C. Collins for assistance and L. Yue and D. Ren for comments on an earlier version of the manuscript. We appreciate the encouragement and helpful comments from other members of the Xu and Clapham laboratories. D.E.C. is founder of Hydra, which is currently working on TRPV3 antagonists. ",

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doi = "10.1016/j.cell.2010.03.013",

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T1 - TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation

AU - Cheng, Xiping

AU - Jin, Jie

AU - Hu, Lily

AU - Shen, Dongbiao

AU - Dong, Xian ping

AU - Samie, Mohammad A.

AU - Knoff, Jayne

AU - Eisinger, Brian

AU - Liu, Mei Ling

AU - Huang, Susan M.

AU - Caterina, Michael J.

AU - Dempsey, Peter

AU - Michael, Lowell Evan

AU - Dlugosz, Andrzej A.

AU - Andrews, Nancy C.

AU - Clapham, David E.

AU - Xu, Haoxing

N1 - Funding Information: This work is supported by HHMI (to N.C.A and D.E.C), startup funds to H.X. from the Department of MCDB and Biological Science Scholar Program, and the University of Michigan and NIH RO1 grants (NS062792 to H.X. and AR045973 to A.A.D.). We thank Dr. Leonidas Tsiokas for the EGFR construct, Dr. Nan Hatch and Dr. Dave Ornitz for the FGFR2 constructs, and Dr. Makato Suzuki for TRPV4 KO mice. We are grateful to Y. Fujiwara (Division of Hematology Transgenic core facility), S. Hein, X. Wang (Rockefeller University), X. Wang, E. Mills, R. Hume, J. Kuwada, M. Akaaboune, and C. Collins for assistance and L. Yue and D. Ren for comments on an earlier version of the manuscript. We appreciate the encouragement and helpful comments from other members of the Xu and Clapham laboratories. D.E.C. is founder of Hydra, which is currently working on TRPV3 antagonists.

PY - 2010/4

Y1 - 2010/4

N2 - 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.

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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