Staurosporine drives non-canonical melanocyte maturation by coupling β-catenin signaling to actin-dependent dendrite remodeling

Abstract

Skin pigmentation relies on the coordinated regulation of melanin production and dendritic morphology to ensure effective pigment distribution. While staurosporine is widely used as a proapoptotic agent in malignant cells, its effects on normal human melanocytes have not been fully characterized. Here, we investigated the impact of staurosporine on melanocyte biology and identify it as a potent inducer of non-canonical melanocyte maturation at sub-cytotoxic concentrations. In primary human neonatal melanocytes, staurosporine treatment enhances melanogenesis and promotes pronounced dendritic remodeling, leading to functional maturation distinct from its apoptotic effects in melanoma cells. Phenotypic analyses demonstrate increased pigment production and expanded dendritic networks that support efficient pigmentation. Molecular characterization indicates that these effects are associated with coordinated activation of {beta}-catenin signaling and actin-dependent cytoskeletal remodeling. The physiological relevance of these findings was further examined in vivo. Topical application of staurosporine to normal guinea pig skin increased baseline pigmentation without detectable inflammation. In addition, staurosporine accelerated repigmentation in a rhododendrol-induced leukoderma model by restoring functionally mature melanocyte populations and enhancing nuclear localization of {beta}-catenin. Together, these results identify staurosporine as a non-canonical modulator of melanocyte maturation and highlight the coordinated regulation of pigment production and dendritic remodeling as a key process supporting pigmentation in acquired hypopigmentary conditions. SummaryO_LIStaurosporine promotes non-canonical maturation of human melanocytes at sub-cytotoxic concentrations. C_LIO_LITreatment enhances both melanogenesis and dendritic remodeling, supporting functional pigmentation. C_LIO_LIStaurosporine increases baseline skin pigmentation in vivo without inducing inflammation. C_LIO_LIRepigmentation is accelerated in a rhododendrol-induced leukoderma model through restoration of mature melanocyte populations. C_LIO_LIThese findings highlight coordinated regulation of pigment production and dendritic morphology as a potential strategy to promote pigmentation in acquired hypopigmentary conditions. C_LI SignificanceLoss of melanocyte dendricity and functional maturation is a shared feature of multiple acquired hypopigmentary disorders, including vitiligo and chemical-induced leukoderma. This study demonstrates that staurosporine promotes dendritic remodeling and pigmentation in normal human melanocytes and enhances repigmentation in vivo. By identifying a melanocyte-intrinsic, ultraviolet-independent maturation program, our findings provide a biological framework for strategies aimed at restoring functional melanocytes in depigmented skin.