Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Glucagon Receptor-mediated Regulation of Gluconeogenic Gene Transcription is Endocytosis-dependent in Primary Hepatocytes

Jan Mikhale B. Cajulao, Mark E. von Zastrow, Erica L. Sanchez
doi: https://doi.org/10.1101/2021.09.03.458925
Jan Mikhale B. Cajulao
1San Francisco State University, Department of Biology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark E. von Zastrow
2University of California San Francisco, Department of Psychiatry
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erica L. Sanchez
1San Francisco State University, Department of Biology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: elsanchez09@sfsu.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

A number of G protein-coupled receptors (GPCRs) are now thought to use endocytosis to promote cellular cAMP signaling that drives downstream transcription of cAMP-dependent genes. We tested if this is true for the Glucagon Receptor (GCGR), which mediates physiological regulation of hepatic glucose metabolism via cAMP signaling. We show that epitope-tagged GCGRs undergo clathrin and dynamin-dependent endocytosis in HEK293 cells after activation by glucagon, and transit via EEA1-marked endosomes shown previously to be sites of GPCR/Gs-stimulated production of cAMP. We further show that endocytosis potentiates cytoplasmic cAMP elevation produced by GCGR activation and promotes transcription of PCK1, the gene which encodes the enzyme catalyzing the rate-limiting step in gluconeogenesis. We verify endocytosis-dependent induction of PCK1 expression by endogenous GCGRs in primary hepatocytes, and show similar control of two other gluconeogenic genes (PGC1α and G6PC). Together, these results implicate the endosomal signaling paradigm in metabolic regulation by glucagon.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted September 04, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Glucagon Receptor-mediated Regulation of Gluconeogenic Gene Transcription is Endocytosis-dependent in Primary Hepatocytes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Glucagon Receptor-mediated Regulation of Gluconeogenic Gene Transcription is Endocytosis-dependent in Primary Hepatocytes
Jan Mikhale B. Cajulao, Mark E. von Zastrow, Erica L. Sanchez
bioRxiv 2021.09.03.458925; doi: https://doi.org/10.1101/2021.09.03.458925
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Glucagon Receptor-mediated Regulation of Gluconeogenic Gene Transcription is Endocytosis-dependent in Primary Hepatocytes
Jan Mikhale B. Cajulao, Mark E. von Zastrow, Erica L. Sanchez
bioRxiv 2021.09.03.458925; doi: https://doi.org/10.1101/2021.09.03.458925

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4239)
  • Biochemistry (9172)
  • Bioengineering (6804)
  • Bioinformatics (24064)
  • Biophysics (12155)
  • Cancer Biology (9564)
  • Cell Biology (13825)
  • Clinical Trials (138)
  • Developmental Biology (7658)
  • Ecology (11737)
  • Epidemiology (2066)
  • Evolutionary Biology (15541)
  • Genetics (10672)
  • Genomics (14359)
  • Immunology (9511)
  • Microbiology (22901)
  • Molecular Biology (9129)
  • Neuroscience (49113)
  • Paleontology (357)
  • Pathology (1487)
  • Pharmacology and Toxicology (2583)
  • Physiology (3851)
  • Plant Biology (8351)
  • Scientific Communication and Education (1473)
  • Synthetic Biology (2301)
  • Systems Biology (6205)
  • Zoology (1302)