A biosensor platform for scalable and live detection of PYY hormone production from
enteroendocrine cells with single-event resolution
enteroendocrine cells with single-event resolution
File(s)
Published version
Author(s)
Hanyaloglu, Aylin
Frost, Gary
Aanya, Hirdaramani
Type
Journal Article
Abstract
Peptide YY (PYY) comprises the secretory repertoire of enteroendocrine L-cells alongside glucagon-like peptide-1 (GLP-1), and positively modulates postprandial satiety, digestion mechanics, and regeneration of the intestinal epithelium. Whereas immortalised GLP-1-secreting human L-cell models support pre-clinical drug discovery, comparable human lines that robustly secrete PYY are lacking, hindering mechanistic studies of its release. We present a biosensor for detection of PYY production and secretion from human enteroendocrine cells in vitro. Guided by in silico structural prediction, we engineer a superecliptic phluorin (SEP)-tagged PYY, SEP-PYY, that engages native hormone processing machinery and is responsive to canonical nutrient stimuli when expressed in a human enteroendocrine-like cell line, NCI-H716. SEP-PYY production and secretion can be measured by flow cytometry and spectrofluorometric plate readouts respectively, methods with superior time- and cost-efficacy to current hormone detection methods. Leveraging the pH sensitivity of SEP, we use this biosensor in detection of single-event hormone exocytosis by total internal reflection microscopy. Finally, we demonstrate the application of our platform in screening ligands of metabolite-sensing G-protein coupled receptors that drive SEP-PYY secretion, supporting discovery of druggable and nutrient-driven pathways in metabolic disease.
Date Issued
2026-09-01
Date Acceptance
2026-07-08
Citation
Journal of Biological Chemistry, 2026, 302 (9)
ISSN
0021-9258
Publisher
Elsevier
Journal / Book Title
Journal of Biological Chemistry
Volume
302
Issue
9
Copyright Statement
© 2026 The Author(s). Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.jbc.2026.113367
Publication Status
Published
Article Number
113367
Date Publish Online
2026-07-24