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CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1.
- Source :
-
The Journal of cell biology [J Cell Biol] 2006 Nov 20; Vol. 175 (4), pp. 563-9. Date of Electronic Publication: 2006 Nov 13. - Publication Year :
- 2006
-
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.
- Subjects :
- Basement Membrane cytology
Cell Adhesion
Connective Tissue Growth Factor
Discoidin Domain Receptor 1
Gene Expression
Gene Expression Regulation
Humans
Immediate-Early Proteins deficiency
Immediate-Early Proteins genetics
Intercellular Signaling Peptides and Proteins deficiency
Intercellular Signaling Peptides and Proteins genetics
Keratinocytes cytology
Nephroblastoma Overexpressed Protein
RNA, Messenger genetics
RNA, Messenger metabolism
Cell Movement
Immediate-Early Proteins metabolism
Intercellular Signaling Peptides and Proteins metabolism
Melanocytes cytology
Receptor Protein-Tyrosine Kinases metabolism
Skin cytology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9525
- Volume :
- 175
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 17101694
- Full Text :
- https://doi.org/10.1083/jcb.200602132