| First Author | Tabone-Eglinger S | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 9 | Pages | 3738-53 |
| PubMed ID | 22637532 | Mgi Jnum | J:186166 |
| Mgi Id | MGI:5431149 | Doi | 10.1096/fj.12-206045 |
| Citation | Tabone-Eglinger S, et al. (2012) Membrane-bound Kit ligand regulates melanocyte adhesion and survival, providing physical interaction with an intraepithelial niche. FASEB J 26(9):3738-53 |
| abstractText | 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. |
