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

Author:

Fukunaga-Kalabis Mizuho1,Martinez Gabriela1,Liu Zhao-Jun1,Kalabis Jiri1,Mrass Paul2,Weninger Wolfgang2,Firth Sue M.3,Planque Nathalie4,Perbal Bernard4,Herlyn Meenhard1

Affiliation:

1. Molecular and Cellular Oncogenesis Program

2. Immunology Program, The Wistar Institute, Philadelphia, PA 19104

3. Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards NSW 2065, Australia

4. Laboratoire d'Oncologie Virale et Moléculaire, Université Paris, 75005 Paris, France

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 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.

Publisher

Rockefeller University Press

Subject

Cell Biology

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