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; Jonathan Z Long

doi:10.1101/2023.06.02.543503

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

bioRxiv [Preprint]. 2023 Jun 7:2023.06.02.543503. doi: 10.1101/2023.06.02.543503.

Authors

Amanda L Wiggenhorn^{1

2

3

4}, Hind Z Abuzaid^{1

3}, Laetitia Coassolo¹, Veronica L Li^{1

2

3

4}, Julia T Tanzo^{1

3}, Wei Wei^{1

5

3}, Xuchao Lyu^{1

3

4}, Katrin J Svensson^{1

6}, Jonathan Z Long^{1

2

3

6

4}

Affiliations

¹ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Chemistry, Stanford University, Stanford, CA, USA.
³ Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
⁴ Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA.
⁵ Department of Biology, Stanford University, Stanford, CA, USA.
⁶ Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA.

Abstract

Peptide hormones and neuropeptides are fundamental signaling molecules that control diverse aspects of mammalian homeostasis and physiology. Here we demonstrate the endogenous presence of a sequence diverse class of orphan, 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 regulation in blood plasma by diverse environmental and physiologic stimuli. One capped peptide, CAP-TAC1, is a tachykinin neuropeptide-like molecule and a nanomolar agonist of multiple mammalian tachykinin receptors. A second capped peptide, CAP-GDF15, is a 12-mer peptide that reduces food intake and body weight. Capped peptides therefore define a largely unexplored class of circulating molecules with potential to regulate cell-cell communication in mammalian physiology.

Keywords: Peptides; genomic; hormones; intercellular; mass spectrometry; neuropeptides; physiology; signaling; tachykinin.

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Abstract

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