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Quezada, E. ; Knoch, K.-P. ; Vasiljevic, J. ; Seiler, A. ; Pal, A.* ; Gunasekaran, A. ; Münster, C. ; Friedland, D. ; Schöniger, E. ; Sönmez, A. ; Roch, P. ; Wegbrod, C. ; Ganß, K. ; Kipke, N. ; Alberti, S.* ; Nano, R.* ; Piemonti, L.* ; Aust, D.* ; Weitz, J. ; Distler, M. ; Solimena, M.

Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells.

EMBO J., DOI: 10.1038/s44318-025-00448-7 (2025)
Verlagsversion Forschungsdaten DOI PMC
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Upregulation of insulin mRNA translation upon hyperglycemia in pancreatic islet β-cells involves several RNA-binding proteins. Here, we found that G3BP1, a stress granule marker downregulated in islets of subjects with type 2 diabetes, binds to insulin mRNA in glucose concentration-dependent manner. We show in mouse insulinoma MIN6-K8 cells exposed to fasting glucose levels that G3BP1 and its paralog G3BP2 colocalize to cytosolic condensates with eIF3b, phospho-AMPKαThr172 and Ins1/2 mRNA. Glucose stimulation dissolves G3BP1+/2+ condensates with cytosolic redistribution of their components. The aldolase inhibitor aldometanib prevents the glucose- and pyruvate-induced dissolution of G3BP1+/2+ condensates, increases phospho-AMPKαThr172 levels and reduces those of phospho-mTORSer2448. G3BP1 or G3BP2 depletion precludes condensate assembly. KO of G3BP1 decreases Ins1/2 mRNA abundance and translation as well as proinsulin levels, and impaires glucose-stimulated insulin secretion. Further, other insulin secretagogues such as exendin-4 and palmitate, but not high KCl, prompts the dissolution of G3BP1+/2+ condensates. G3BP1+/2+/Ins mRNA+ condensates are also found in primary mouse and human β-cells. Hence, G3BP1+/2+ condensates represent a conserved glycolysis/aldolase-regulated compartment for the physiological storage and protection of insulin mRNA in resting β-cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Diabetes ; Insulin ; Islet ; Stress Granules ; Translation; Endoplasmic-reticulum Stress; Pancreatectomized Patients; Gene-expression; Quality-control; Glucose; Granules; Translation; Mechanism; Apoptosis; Phosphorylation
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Verlag Wiley
Verlagsort Heidelberg, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)