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Updated: May 11, 2026
08:04
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
PRMT5 modulates the metabolic response to fasting signals
Wen-Wei Tsai1, Sherry Niessen, Naomi Goebel
1The Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037, USA.
Summary
Glucagon promotes glucose production by activating CREB and CRTC2. Protein arginine methyltransferase 5 (PRMT5) links CRTC2 to CREB, enhancing phosphorylation and hepatic gluconeogenesis via epigenetic changes.
Area of Science:
- Molecular Endocrinology
- Epigenetics
- Metabolic Regulation
Background:
- Glucagon maintains glucose balance via hepatic gluconeogenesis, involving cAMP pathway activation.
- cAMP response element binding (CREB) protein and CREB regulated transcriptional coactivator 2 (CRTC2) are key regulators of gluconeogenic gene expression.
- Increased CREB and CRTC2 activity contributes to hyperglycemia in insulin resistance.
Purpose of the Study:
- To investigate the coordinate regulation of CREB and CRTC2 by glucagon.
- To elucidate the mechanism by which CRTC2 influences CREB phosphorylation.
- To determine the role of protein arginine methyltransferase 5 (PRMT5) in this pathway.
Main Methods:
- Investigated the association between CRTC2 and PRMT5 following glucagon activation.
- Assessed the impact of PRMT5 on CREB phosphorylation.
- Examined PRMT5-mediated histone modifications and their effect on chromatin accessibility at gluconeogenic promoters.
- Studied the effect of PRMT5 depletion on hepatic glucose production and gene expression.
Main Results:
- CRTC2 enhances CREB phosphorylation through interaction with PRMT5.
- PRMT5 stimulates CREB phosphorylation via histone H3 Arg2 methylation, increasing chromatin accessibility.
- Depletion of PRMT5 reduces hepatic glucose production and gluconeogenic gene expression.
Conclusions:
- PRMT5 acts as a crucial link between CRTC2 and CREB, mediating glucagon's effect on gluconeogenesis.
- PRMT5 regulates hepatic glucose production through epigenetic modifications that impact transcription factor activity.
- This study reveals a novel mechanism linking chromatin modification to hormonal regulation of metabolic pathways.
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