Scientific article

Membrane-bound Kit ligand regulates melanocyte adhesion and survival, providing physical interaction with an intraepithelial niche

Published inThe FASEB journal, vol. 26, no. 9, p. 3738-3753
Publication date2012

Morphogenesis, as illustrated by melanocyte migration and homing to the skin, requires cadherin adhesion, integrin-dependent migration and Kit-ligand growth factor signaling. However, it is not known how Kit ligand regulates integrin or cadherin-dependent intraepidermal melanocyte behavior. To answer this question, we developed specific 2-dimensional (2D) and 3D culture systems analyzing how soluble or immobilized Kit-ligand-regulated melanocyte migration on vitronectin and laminin, or within a monolayer of kidney epithelial cells. In a 2D system, soluble Kit ligand stimulated integrin-dependent melanoblast migration and chemotaxis and accelerated integrin turnover. In contrast, immobilized, but not soluble, Kit ligand, enhanced integrin-dependent melanocyte spreading on suboptimal laminin concentrations. In 3D, membrane-bound Kit ligand induced intraepithelial melanocyte proliferation, survival, and tight adhesion to epithelial cells, while cleavable Kit ligand was less effective. In contrast, melanocyte motility was independent of membrane-bound Kit ligand, but increased in the presence of the cleavable Kit-ligand isoform. Transmembrane-dimerization or basolateral-targeting mutants of Kit ligand altered intraepithelial melanocyte localization, survival, and adhesion to epithelial cells. These data and the identification of c-kit/Kit-ligand clusters at cell contacts suggest that membrane-bound Kit ligand captures cell surface-expressed c-kit, providing mechanical anchoring and survival signaling within intraepithelial niches, and thereby defining a new mechanism for melanocyte homeostasis and requirement for environmental niches.

Citation (ISO format)
TABONE-EGLINGER, Séverine et al. Membrane-bound Kit ligand regulates melanocyte adhesion and survival, providing physical interaction with an intraepithelial niche. In: The FASEB journal, 2012, vol. 26, n° 9, p. 3738–3753. doi: 10.1096/fj.12-206045
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Article (Published version)
ISSN of the journal0892-6638

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