Proteomic analysis of skin defensive factors of tree frog Hyla simplex

Tree frogs produce a variety of skin defensive chemicals against many biotic and abiotic risk factors for their everyday survival. By proteomics or peptidomics and coupling transcriptome analysis with pharmacological testings, 27 peptides or proteins belonging to 9 families, which act mainly as defensive functions, were identified and characterized from skin secretions of the tree frog, Hyla simplex. They are: (1) a novel family of peptides with EGF- and VEGF-releasing activities; (2) a novel family of analgesic peptides; (3) a family of neurotoxins acting on sodium channel; (4) a snake venom-like presynaptically active neurotoxin; (5) a snake venom-like neurotoxin targeting cyclic nucleotide-gated ion channels; (6) a tachykinin-like peptide, which is the first report from tree frogs; (7) two antimicrobial peptides; (8) a alpha-1-antitrypsin-like serpin; and (9) a wasp venom-like toxin with serine protease inhibitors activity. Families of 1, 2, 4, 5, and 8 proteins or peptides are first reported in amphibians. The chemical array in the tree frog skin shares some similarities with snake venoms. Most of these components in this tree frog help defend against predators, heal wounds, or attenuate suffering.