Pumiliotoxin metabolism and molecular physiology in a poison frog

Poison frogs bioaccumulate alkaloids for chemical defense from their arthropod diet. These small molecules are sequestered from their gastrointestinal tract and transported to the skin for storage. Although many alkaloids are accumulated without modification, some poison frog species can metabolize pumiliotoxin (PTX 251D) into the more potent allopumiliotoxin (aPTX 267A). Despite extensive research characterizing the chemical arsenal of poison frogs, the physiological mechanisms involved in the sequestration and metabolism of individual alkaloids is unknown. We performed a feeding experiment with the Dyeing poison frog (Dendrobates tinctorius) to ask if this species can metabolize PTX 251D into aPTX 267A and what gene expression changes are associated with PTX 251D exposure in the intestines, liver, and skin. We found that D. tinctorius can metabolize PTX 251D into aPTX 267A, and that PTX 251D exposure changed the expression of genes involved in immune system function and small molecule metabolism and transport. These results show that individual alkaloids can modify gene expression across poison frog tissues and suggest that different alkaloid classes in wild diets may induce specific physiological changes for accumulation and metabolism.