Glycogen Synthase Kinase 3 Beta Controls Presenilin-1-Mediated Endoplasmic Reticulum Ca²⁺ Leak Directed to Mitochondria in Pancreatic Islets and β-Cells.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Christiane KlecWolfgang F Graier

Abstract

In pancreatic β-cells, the intracellular Ca²⁺ homeostasis is an essential regulator of the cells major functions. The endoplasmic reticulum (ER) as interactive intracellular Ca²⁺ store balances cellular Ca²⁺. In this study basal ER Ca²⁺ homeostasis was evaluated in order to reveal potential β-cell-specificity of ER Ca²⁺ handling and its consequences for mitochondrial Ca²⁺, ATP and respiration. The two pancreatic cell lines INS-1 and MIN-6, freshly isolated pancreatic islets, and the two non-pancreatic cell lines HeLA and EA.hy926 were used. Cytosolic, ER and mitochondrial Ca²⁺ and ATP measurements were performed using single cell fluorescence microscopy and respective (genetically-encoded) sensors/dyes. Mitochondrial respiration was monitored by respirometry. GSK3β activity was measured with ELISA. An atypical ER Ca²⁺ leak was observed exclusively in pancreatic islets and β-cells. This continuous ER Ca²⁺ efflux is directed to mitochondria and increases basal respiration and organellar ATP levels, is established by GSK3β-mediated phosphorylation of presenilin-1, and is prevented by either knockdown of presenilin-1 or an inhibition/knockdown of GSK3β. Expression of a presenlin-1 mutant that mimics GSK3β-mediated phosphorylation e...Continue Reading

Citations

Oct 30, 2019·The FEBS Journal·Corina T Madreiter-SokolowskiWolfgang F Graier
May 22, 2019·Nature Cell Biology·Roland Malli, Wolfgang F Graier
Aug 10, 2019·Contact·Corina T Madreiter-SokolowskiWolfgang F Graier
Dec 11, 2019·International Journal of Molecular Sciences·Christiane KlecWolfgang F Graier
Apr 23, 2020·Science Signaling·Neeharika NemaniMuniswamy Madesh
Feb 23, 2020·Seminars in Cell & Developmental Biology·Olof Idevall-Hagren, Anders Tengholm
Mar 9, 2021·Trends in Cell Biology·Jens LonckeGeert Bultynck
Sep 23, 2020·Cell Calcium·Eleni Georgiadou, Guy A Rutter
Apr 4, 2021·International Journal of Molecular Sciences·Anna WeiserUmberto De Marchi
Apr 3, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Fernanda O LemosJan B Parys
May 19, 2020·The Journal of Physical Chemistry. B·Rukmankesh Mehra, Kasper P Kepp

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence imaging
ELISA
transfection
PCR
enzyme-linked immunosorbent assay
Protein

Software Mentioned

GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Related Papers

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Corina T Madreiter-SokolowskiWolfgang F Graier
Pflügers Archiv : European journal of physiology
Andras Spät, Ole H Petersen
Seminars in Cell & Developmental Biology
M C Ashby, A V Tepikin
© 2022 Meta ULC. All rights reserved