LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides. (September 2022)

• Record Type: Journal Article
• Authors: Gulyas, Gergo; Korzeniowski, Marek K.; Eugenio, Carlos Ernesto Bastián; Vaca, Luis; Kim, Yeun Ju; Balla, Tamas
• Is Part Of: Cell calcium. Volume 106(2022)
• Publication Date: 2022-09
• Subjects: Calcium -- Plasma membrane -- ER -- Membrane contact sites -- Lipid transfer proteins -- Phosphatidylinositol -- Phosphoinositides; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2022.102631
• Languages: English
• ISSNs: 0143-4160

Abstract

Highlights: Plasma membrane (PM) association of the ER-localized Ca 2+ regulatory STIM1 protein responds to changes in PM phosphatidylinositol 4-phosphate (PI4P) levels. Ca 2+ -entry via the STIM1-Orai1 complex is inhibited by PI4P depletion even under conditions when PI(4, 5)P2 levels are unchanged. The non-vesicular lipid transfer proteins, ORP3, -5 and -8, that affect PM PI4P levels can regulate Ca 2+ entry via SOCE revealing a close relationship between lipid transport and Ca 2+ entry at ER-PM contact sites. Abstract: The ER-resident proteins STIM1 together with the plasma membrane (PM)-localized Orai1 channels constitute the molecular components of the store-operated Ca 2+ entry (SOCE) pathway. Prepositioning of STIM1 to the peripheral ER close to the PM ensures its efficient interaction with Orai1 upon a decrease in the ER luminal Ca 2+ concentration. The C-terminal polybasic domain of STIM1 has been identified as mediating the interaction with PM phosphoinositides and hence positions the molecule to ER-PM contact sites. Here we show that STIM1 requires PM phosphatidylinositol 4-phosphate (PI4P) for efficient PM interaction. Accordingly, oxysterol binding protein related proteins (ORPs) that work at ER-PM junctions and consume PI4P gradients exert important control over the Ca 2+ entry process. These studies reveal an important connection between non-vesicular lipid transport at ER-PM contact sites and regulation of ER Ca 2+ store refilling. Graphical abstract: Image, graphical abstract