A class of secreted mammalian peptides with potential to expand cell-cell communication

Amanda L. Wiggenhorn, Hind Z. Abuzaid, Laetitia Coassolo, Veronica L. Li, Julia T. Tanzo, Wei Wei, Xuchao Lyu, Katrin J. Svensson and Jonathan Z. Long ()
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Amanda L. Wiggenhorn: Stanford University School of Medicine
Hind Z. Abuzaid: Stanford University School of Medicine
Laetitia Coassolo: Stanford University School of Medicine
Veronica L. Li: Stanford University School of Medicine
Julia T. Tanzo: Stanford University School of Medicine
Wei Wei: Stanford University School of Medicine
Xuchao Lyu: Stanford University School of Medicine
Katrin J. Svensson: Stanford University School of Medicine
Jonathan Z. Long: Stanford University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Peptide hormones and neuropeptides are signaling molecules that control diverse aspects of mammalian homeostasis and physiology. Here we provide evidence for the endogenous presence of a sequence diverse class of blood-borne peptides that we call “capped peptides.” Capped peptides are fragments of secreted proteins and defined by the presence of two post-translational modifications – N-terminal pyroglutamylation and C-terminal amidation – which function as chemical “caps” of the intervening sequence. Capped peptides share many regulatory characteristics in common with that of other signaling peptides, including dynamic physiologic regulation. One capped peptide, CAP-TAC1, is a tachykinin neuropeptide-like molecule and a nanomolar agonist of mammalian tachykinin receptors. A second capped peptide, CAP-GDF15, is a 12-mer peptide cleaved from the prepropeptide region of full-length GDF15 that, like the canonical GDF15 hormone, also reduces food intake and body weight. Capped peptides are a potentially large class of signaling molecules with potential to broadly regulate cell-cell communication in mammalian physiology.

Date: 2023
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DOI: 10.1038/s41467-023-43857-0

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