MELANOCYTIC GALECTIN-3 IS ASSOCIATED WITH TYROSINASE RELATED PROTEIN-1 AND PIGMENT BIOSYNTHESIS

Galectin-3 is a family member of the carbohydrate binding proteins widely expressed by many cell types and exhibits multiple cellular functions. We demonstrate that melanocytes express galectin-3, which is predominantly localized to the cell body peripherally along the Golgi zone. Downregulation of galectin-3 in human melanocytes using shRNA technology resulted in reduction of both melanin synthesis and expression/activity of Tyrp-1. In the cell body, galectin-3 co-localizes with melanosome destined cargo, specifically tyrosinase and tyrosinase-related protein-1. We studied melanocytes cultured from patients with forms of Hermansky-Pudlak syndrome containing defects in trafficking steps governed by BLOC-2 (HPS5), BLOC-3 (HPS1) and adaptin-3 (HPS2). We found galectin-3 expression mimicked the defective expression of the tyrosinase cargo in dendrites of HPS-5 melanocytes, but was not altered in HPS1 or HPS2 melanocytes. In addition, galectin-3 co-localized predominantly with the HPS-5 component of BLOC-2 in normal human melanocytes. These data indicate that galectin-3 is a regulatory component in melanin synthesis affecting the expression of Tyrp-1.