The Open UniversitySkip to content
 

Nicotinic acid adenine dinucleotide phosphate (NAADP) and endolysosomal two-pore channels modulate membrane excitability and stimulus-secretion coupling in mouse pancreatic β cells

Arredouani, Abdelilah; Ruas, Margarida; Collins, Stephan C.; Parkesh, Raman; Clough, Frederick; Pillinger, Toby; Coltart, George; Rietdorf, Katja; Royle, Andrew; Johnson, Paul; Braun, Matthias; Zhang, Quan; Sones, William; Shimomura, Kenju; Morgan, Anthony J.; Lewis, Alexander M.; Chuang, Kai-Ting; Tunn, Ruth; Gadea, Joaquin; Teboul, Lydia; Heister, Paula M.; Tynan, Patricia W.; Bellomo, Elisa A.; Rutter, Guy A.; Rorsman, Patrik; Churchill, Grant C.; Parrington, John and Galione, Antony (2015). Nicotinic acid adenine dinucleotide phosphate (NAADP) and endolysosomal two-pore channels modulate membrane excitability and stimulus-secretion coupling in mouse pancreatic β cells. Journal of Biological Chemistry, 290(35) pp. 21376–21392.

Full text available as:
Full text not publicly available
Due to copyright restrictions, this file is not available for public download
[img]
Preview
PDF (Version of Record) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (4MB) | Preview
Full text not publicly available
Due to copyright restrictions, this file is not available for public download
DOI (Digital Object Identifier) Link: https://doi.org/10.1074/jbc.M115.671248
Google Scholar: Look up in Google Scholar

Abstract

Pancreatic beta cells are electrically excitable, and respond to elevated glucose concentrations with bursts of Ca2+ action potentials due to the activation of voltage-dependent Ca2+ channels (VDCCs) which leads to the exocytosis of insulin granules. We have examined the possible role of NAADP-mediated Ca2+ release from intracellular stores during stimulus-secretion coupling in primary mouse pancreatic beta cells. NAADP-regulated Ca2+ release channels, likely two-pore channels (TPCs), have recently been shown to be a major mechanism for mobilizing Ca2+ from the endo-lysosomal system, resulting in localized Ca2+ signals. We show here that NAADP-mediated Ca2+ release from endolysosomal Ca2+ stores activates inward membrane currents and depolarizes the beta cell to the threshold for VDCC activation and thereby contributes to glucose-evoked depolarization of the membrane potential during stimulus-response coupling. Selective pharmacological inhibition of NAADP-evoked Ca2+ release or genetic ablation of endolysosomal TPC1 or TPC2 channels attenuates glucose- and sulphonylurea-induced membrane currents, depolarization, cytoplasmic Ca2+ signals and insulin secretion. Our findings implicate NAADP-evoked Ca2+ release from acidic Ca2+ storage organelles in stimulus-secretion coupling in beta cells.

Item Type: Journal Item
Copyright Holders: 2015 The American Society for Biochemistry and Molecular Biology
ISSN: 1083-351X
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot SetWellcome Trust
Not SetNot SetMRC
Not SetNot SetThe Royal Society
Keywords: diabetes; endosome; insulin; lysosome; nicotinic acid adenine dinucleotide phosphate (NAADP); TPC1; TPC2
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 44168
Depositing User: Katja Rietdorf
Date Deposited: 25 Aug 2015 09:43
Last Modified: 18 May 2017 03:34
URI: http://oro.open.ac.uk/id/eprint/44168
Share this page:

Altmetrics

Download history for this item

These details should be considered as only a guide to the number of downloads performed manually. Algorithmic methods have been applied in an attempt to remove automated downloads from the displayed statistics but no guarantee can be made as to the accuracy of the figures.

Actions (login may be required)

Policies | Disclaimer

© The Open University   + 44 (0)870 333 4340   general-enquiries@open.ac.uk