Abstract
Soluble adenylyl cyclase (sAC) is a non-canonical, pH-sensitive source of cAMP in mammalian cells. We previously demonstrated that loss of sAC elevates melanosomal pH and increases melanin production, both in vitro and in vivo. An ultrastructural analysis of melanosomes following loss of sAC suggested that sAC inhibition induced melanosome maturation. Since melanosome maturation and changes in pH are associated with melanosome protein processing, we have begun to explore whether sAC activity influences the expression of melanosome proteins. RNAseq analysis of wild-type and knockout sAC melanocytes did not reveal any overt changes in melanosome protein mRNA. However, Western analysis suggests that post-translational modification of melanosome proteins is affected by loss of sAC. The observed change in protein processing is consistent with previous studies using drugs that alter melanosome pH. Thus, in addition to altering pigmentation, sAC regulation of melanosome pH affects the melanosome protein profile.
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