Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar;597(5):657-671.
doi: 10.1002/1873-3468.14580. Epub 2023 Jan 30.

F-actin determines the time-dependent shift in docking dynamics of glucagon-like peptide-1 granules upon stimulation of secretion

Kazuki Harada  1 , Maoko Takashima  1 , Tetsuya Kitaguchi  2 , Takashi Tsuboi  1
Affiliations
Free article

F-actin determines the time-dependent shift in docking dynamics of glucagon-like peptide-1 granules upon stimulation of secretion

Kazuki Harada et al. FEBS Lett. 2023 Mar.
Free article

Abstract

Although exocytosis can be categorized into several forms based on docking dynamics, temporal regulatory mechanisms of the exocytotic forms are unclear. We explored the dynamics of glucagon-like peptide-1 (GLP-1) exocytosis in murine GLUTag cells (GLP-1-secreting enteroendocrine L-cells) upon stimulation with deoxycholic acid (DCA) or high K+ to elucidate the mechanisms regulating the balance between the different types of exocytotic forms (pre-docked with the plasma membrane before stimulation; docked after stimulation and subsequently fused; or rapidly recruited and fused after stimulation, without stable docking). GLP-1 exocytosis showed a biphasic pattern, and we found that most exocytosis was from the pre-docked granules with the plasma membrane before stimulation, or granules rapidly fused to the plasma membrane without docking after stimulation. In contrast, granules docked with the plasma membrane after stimuli and eventually fused were predominant thereafter. Inhibition of actin polymerization suppressed exocytosis of the pre-docked granules. These results suggest that the docking dynamics of GLP-1 granules shows a time-dependent biphasic shift, which is determined by interaction with F-actin.

Keywords: actin; cAMP; calcium; exocytosis; glucagon-like peptide-1; live-cell imaging.

PubMed Disclaimer

References

    1. Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiol Rev 87, 1409-1439.
    1. Zhang T, Perkins MH, Chang H, Han W and de Araujo IE (2022) An inter-organ neural circuit for appetite suppression. Cell 185, 2478-2494.e28.
    1. Trapp S and Brierley DI (2022) Brain GLP-1 and the regulation of food intake: GLP-1 action in the brain and its implications for GLP-1 receptor agonists in obesity treatment. Br J Pharmacol 179, 557-570.
    1. Villhauer EB, Brinkman JA, Naderi GB, Burkey BF, Dunning BE, Prasad K, Mangold BL, Russell ME and Hughes TE (2003) 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 46, 2774-2789.
    1. Kalra S, Das S and Zargar A (2022) A review of oral semaglutide available evidence: a new era of management of diabetes with peptide in a pill form. Indian J Endocrinol Metab 26, 98-105.

Publication types

Associated data

LinkOut - more resources