Teneurin C-terminal associated peptides (TCAPs) are a family of highly conserved 40âÂÂ41 amino acid peptides encoded within the C-terminus of the type II transmembrane proteins known as teneurins that are involved with cell adhesion. TCAPs are liberated by proteolytic cleavage from the parent protein. Once released, TCAPs act as soluble neuromodulatory and metabolic regulators that influence neuronal morphology, synaptic connectivity, and stress responsiveness, in part via cytoskeletal remodeling, enhanced energy generating oxidative metabolism, and functional interaction with adhesion GPCRs of the latrophilin family.
Across vertebrates, four paralogous TCAPs (TCAP-1âÂÂ4) exhibit structural similarity to corticotropin-releasing hormone (CRH) and other secretin-family peptides and have been shown in rodent and non-mammalian models to exert anxiolytic-like effects, modulate glucose and energy homeostasis, and participate in broader tissue-specific signaling, highlighting TCAPs as evolutionarily conserved peptides.
TCAPs are potential starting points for neuropsychiatric and metabolic disease therapeutics.
TCAP peptides are encoded at the distal CâÂÂterminus of teneurins, where they are bounded by an NâÂÂterminal prohormone convertaseâÂÂlike Lys/Arg cleavage site and a CâÂÂterminal glycineâÂÂbasic amidation motif (e.g. GKR/GRR) immediately before the stop codon, consistent with proteolytic release and subsequent CâÂÂterminal amidation by peptidylglycine alpha-amidating monooxygenase.