Topobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesis.

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.

• Authors: Liat Samuelov, Eli Sprecher, Koji Sugawara, Suman K Singh, Desmond J Tobin, Daisuke Tsuruta, Tamás Bíró, Jennifer E Kloepper, Ralf Paus
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 133 Issue 6 Pg. 1591-600 (Jun 2013) ISSN: 1523-1747 [Electronic] United States
• PMID: 23334344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• MITF protein, human
• Melanins
• Microphthalmia-Associated Transcription Factor
• Stem Cell Factor
• gp100 Melanoma Antigen
• Monophenol Monooxygenase
• Proto-Oncogene Proteins c-kit
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3

Topics

• Cadherins (genetics, metabolism)
• Cells, Cultured
• Enzyme Activation (physiology)
• Epidermal Cells
• Epidermis (physiology)
• Gene Knockdown Techniques
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Hair Follicle (cytology, physiology)
• Humans
• Melanins (biosynthesis)
• Melanocytes (cytology, physiology)
• Microphthalmia-Associated Transcription Factor (metabolism)
• Monophenol Monooxygenase (genetics, metabolism)
• Proto-Oncogene Proteins c-kit (metabolism)
• Skin Pigmentation (physiology)
• Stem Cell Factor (metabolism)
• Wnt Signaling Pathway (physiology)
• gp100 Melanoma Antigen (genetics, metabolism)