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

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 lifelong stable ratio. In this study, we report that coculturing melanocytes with keratinocytes up-regulated CCN3...

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Veröffentlicht in:The Journal of cell biology 2006-11, Vol.175 (4), p.563-569
Hauptverfasser: Fukunaga-Kalabis, Mizuho, Martinez, Gabriela, Liu, Zhao-Jun, Kalabis, Jiri, Mrass, Paul, Weninger, Wolfgang, Firth, Sue M, Planque, Nathalie, Perbal, Bernard, Herlyn, Meenhard
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container_end_page 569
container_issue 4
container_start_page 563
container_title The Journal of cell biology
container_volume 175
creator Fukunaga-Kalabis, Mizuho
Martinez, Gabriela
Liu, Zhao-Jun
Kalabis, Jiri
Mrass, Paul
Weninger, Wolfgang
Firth, Sue M
Planque, Nathalie
Perbal, Bernard
Herlyn, Meenhard
description 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 lifelong 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.
doi_str_mv 10.1083/jcb.200602132
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subjects Atoms & subatomic particles
Basement membrane
Basement Membrane - cytology
Cell Adhesion
Cell growth
Cell lines
Cell Movement
Coculture techniques
Collagens
Connective Tissue Growth Factor
Discoidin Domain Receptor 1
Gene Expression
Gene Expression Regulation
Humans
Immediate-Early Proteins - deficiency
Immediate-Early Proteins - genetics
Immediate-Early Proteins - metabolism
Intercellular Signaling Peptides and Proteins - deficiency
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Keratinocytes
Keratinocytes - cytology
Melanocytes
Melanocytes - cytology
Membranes
Nephroblastoma Overexpressed Protein
Receptor Protein-Tyrosine Kinases - metabolism
Receptors
RNA, Messenger - genetics
RNA, Messenger - metabolism
Skin
Skin - cytology
Small interfering RNA
Stem cells
Studies
title CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1
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