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:10.1038/s41467-023-43857-0

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

Nat Commun. 2023 Dec 8;14(1):8125. doi: 10.1038/s41467-023-43857-0.

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

3

5}, Xuchao Lyu^{1

3

4}, Katrin J Svensson^{1

6}, Jonathan Z Long^{7

8

9

10

11}

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.
⁷ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.
⁸ Department of Chemistry, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.
⁹ Sarafan ChEM-H, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.
¹⁰ Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.
¹¹ Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.

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.

MeSH terms

Animals
Cell Communication
Mammals / metabolism
Neuropeptides* / metabolism
Peptide Hormones* / metabolism
Protein Processing, Post-Translational
Tachykinins / metabolism

Substances

Neuropeptides
Tachykinins
Peptide Hormones

Abstract

MeSH terms

Substances

Grants and funding