1240 Distinct cAMP signaling microdomains differentially regulate melanosomal pH and pigmentation

cAMP signaling is well-established in the regulation of melanin synthesis. Two distinct pathways, melanocortin 1 receptor (MC1R) and soluble adenylyl cyclase (sAC) are known to differentially modulate melanogenesis. The MC1R pathway control melanogenesis via gene expression, while sAC influences synthesis melanosomal pH. However, whether affects pH remained unclear. Using human mouse melanocytes lacking signaling, we show that loss does not alter Further, require active either or melanocytes. Thus, appears be only involved regulation. Since function stimulates wild type melanocytes, also asked if sAC-dependent found has no effect on skin hair content null (e/e) mice. Interestingly, application forskolin, which activates downstream increase epidermal eumelanin e/e mice, leads greater enhancement production knockout mice relative MC1R- pathways define mechanisms regulate pigmentation.