CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1

Mizuho Fukunaga-Kalabis, Gabriela Martinez, Zhao-Jun Liu, Jiri Kalabis, Paul Mrass, Wolfgang Weninger, Sue M. Firth, Nathalie Planque, Bernard Perbal, Meenhard Herlyn

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Melanocytes reside within the basal layer of the human epidermis, where they attach to the basement membrane and replicate at a rate proportionate to that of keratinocytes, maintaining a life-long stable ratio. In this study, we report that coculturing melanocytes with keratinocytes up-regulated CCN3, a matricellular protein that we subsequently found to be critical for the spatial localization of melanocytes to the basement membrane. CCN3 knockdown cells were dissociated either upward to the suprabasal layers of the epidermis or downward into the dermis. The overexpression of CCN3 increased adhesion to collagen type IV, the major component of the basement membrane. As the receptor responsible for CCN3-mediated melanocyte localization, we identified discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that acts as a collagen IV adhesion receptor. DDR1 knockdown decreased melanocyte adhesion to collagen IV and shifted melanocyte localization in a manner similar to CCN3 knockdown. These results demonstrate an intricate and necessary communication between keratinocytes and melanocytes in maintaining normal epidermal homeostasis.

Original languageEnglish
Pages (from-to)563-569
Number of pages7
JournalJournal of Cell Biology
Volume175
Issue number4
DOIs
StatePublished - Nov 20 2006
Externally publishedYes

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Melanocytes
Skin
Keratinocytes
Basement Membrane
Epidermis
Collagen
Collagen Type IV
Receptor Protein-Tyrosine Kinases
Dermis
Discoidin Domain Receptor 1
Homeostasis
Communication
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Fukunaga-Kalabis, M., Martinez, G., Liu, Z-J., Kalabis, J., Mrass, P., Weninger, W., ... Herlyn, M. (2006). CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. Journal of Cell Biology, 175(4), 563-569. https://doi.org/10.1083/jcb.200602132

CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. / Fukunaga-Kalabis, Mizuho; Martinez, Gabriela; Liu, Zhao-Jun; Kalabis, Jiri; Mrass, Paul; Weninger, Wolfgang; Firth, Sue M.; Planque, Nathalie; Perbal, Bernard; Herlyn, Meenhard.

In: Journal of Cell Biology, Vol. 175, No. 4, 20.11.2006, p. 563-569.

Research output: Contribution to journalArticle

Fukunaga-Kalabis, M, Martinez, G, Liu, Z-J, Kalabis, J, Mrass, P, Weninger, W, Firth, SM, Planque, N, Perbal, B & Herlyn, M 2006, 'CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1', Journal of Cell Biology, vol. 175, no. 4, pp. 563-569. https://doi.org/10.1083/jcb.200602132
Fukunaga-Kalabis M, Martinez G, Liu Z-J, Kalabis J, Mrass P, Weninger W et al. CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. Journal of Cell Biology. 2006 Nov 20;175(4):563-569. https://doi.org/10.1083/jcb.200602132
Fukunaga-Kalabis, Mizuho ; Martinez, Gabriela ; Liu, Zhao-Jun ; Kalabis, Jiri ; Mrass, Paul ; Weninger, Wolfgang ; Firth, Sue M. ; Planque, Nathalie ; Perbal, Bernard ; Herlyn, Meenhard. / CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. In: Journal of Cell Biology. 2006 ; Vol. 175, No. 4. pp. 563-569.
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