Topobiology of human pigmentation

P-cadherin selectively stimulates hair follicle melanogenesis

Liat Samuelov, Eli Sprecher, Koji Sugawara, Suman K. Singh, Desmond J. Tobin, Daisuke Tsuruta, T. Bíró, Jennifer E. Kloepper, Ralf Paus

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

P-cadherin serves as a major topobiological cue in mammalian epithelium. In human hair follicles (HFs), it is prominently expressed in the inner hair matrix that harbors the HF pigmentary unit. However, the role of P-cadherin in normal human pigmentation remains unknown. As patients with mutations in the gene that encodes P-cadherin show hypotrichosis and fair hair, we explored the hypothesis that P-cadherin may control HF pigmentation. When P-cadherin was silenced in melanogenically active organ-cultured human scalp HFs, this significantly reduced HF melanogenesis and tyrosinase activity as well as gene and/or protein expression of gp100, stem cell factor, c-Kit, and microphthalmia-associated transcription factor (MITF), both in situ and in isolated human HF melanocytes. Instead, epidermal pigmentation was unaffected by P-cadherin knockdown in organ-cultured human skin. In hair matrix keratinocytes, P-cadherin silencing reduced plasma membrane β-catenin, whereas glycogen synthase kinase 3 beta (GSK3β) and phospho-β-catenin expression were significantly upregulated. This suggests that P-cadherin-GSK3β/Wnt signaling is required for maintaining the expression of MITF to sustain intrafollicular melanogenesis. Thus, P-cadherin-mediated signaling is a melanocyte subtype-specific topobiological regulator of normal human pigmentation, possibly via GSK3β-mediated canonical Wnt signaling.

Original languageEnglish
Pages (from-to)1591-1600
Number of pages10
JournalJournal of Investigative Dermatology
Volume133
Issue number6
DOIs
Publication statusPublished - Jun 2013

Fingerprint

Hair Follicle
Pigmentation
Cadherins
Glycogen Synthase Kinase 3
Microphthalmia-Associated Transcription Factor
Catenins
Melanocytes
Hair
Hypotrichosis
Genes
Stem Cell Factor
Monophenol Monooxygenase
beta Catenin
Cell membranes
Ports and harbors
Scalp
Keratinocytes
Cues
Skin
Epithelium

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Samuelov, L., Sprecher, E., Sugawara, K., Singh, S. K., Tobin, D. J., Tsuruta, D., ... Paus, R. (2013). Topobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesis. Journal of Investigative Dermatology, 133(6), 1591-1600. https://doi.org/10.1038/jid.2013.18

Topobiology of human pigmentation : P-cadherin selectively stimulates hair follicle melanogenesis. / Samuelov, Liat; Sprecher, Eli; Sugawara, Koji; Singh, Suman K.; Tobin, Desmond J.; Tsuruta, Daisuke; Bíró, T.; Kloepper, Jennifer E.; Paus, Ralf.

In: Journal of Investigative Dermatology, Vol. 133, No. 6, 06.2013, p. 1591-1600.

Research output: Contribution to journalArticle

Samuelov, L, Sprecher, E, Sugawara, K, Singh, SK, Tobin, DJ, Tsuruta, D, Bíró, T, Kloepper, JE & Paus, R 2013, 'Topobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesis', Journal of Investigative Dermatology, vol. 133, no. 6, pp. 1591-1600. https://doi.org/10.1038/jid.2013.18
Samuelov, Liat ; Sprecher, Eli ; Sugawara, Koji ; Singh, Suman K. ; Tobin, Desmond J. ; Tsuruta, Daisuke ; Bíró, T. ; Kloepper, Jennifer E. ; Paus, Ralf. / Topobiology of human pigmentation : P-cadherin selectively stimulates hair follicle melanogenesis. In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 6. pp. 1591-1600.
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