Oxysterol-binding protein related-proteins (ORPs) 5 and 8 regulate calcium signaling at specific cell compartments

Cell Calcium
Ilari PulliKid Törnquist

Abstract

Oxysterol-binding protein related-protein 5 and 8 (ORP5/8) localize to the membrane contact sites (MCS) of the endoplasmic reticulum (ER) and the mitochondria, as well as to the ER-plasma membrane (PM) MCS. The MCS are emerging as important regulators of cell signaling events, including calcium (Ca2+) signaling. ORP5/8 have been shown to interact with phosphatidylinositol-4,5-bisphosphate (PIP2) in the PM, and to modulate mitochondrial respiration and morphology. PIP2 is the direct precursor of inositol trisphosphate (IP3), a key second messenger responsible for Ca2+-release from the intracellular Ca2+ stores. Further, mitochondrial respiration is linked to Ca2+ transfer from the ER to the mitochondria. Hence, we asked whether ORP5/8 would affect Ca2+ signaling in these cell compartments, and employed genetically engineered aequorin Ca2+ probes to investigate the effect of ORP5/8 in the regulation of mitochondrial and caveolar Ca2+. Our results show that ORP5/8 overexpression leads to increased mitochondrial matrix Ca2+ as well as to increased Ca2+ concentration at the caveolar subdomains of the PM during histamine stimulation, while having no effect on the cytoplasmic Ca2+. Also, we found that ORP5/8 overexpression increases c...Continue Reading

Citations

Jan 19, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mengyang XuDaoguang Yan
Aug 17, 2019·EMBO Reports·Isabel Gordaliza-AlagueroAntonio Zorzano
Mar 27, 2020·International Journal of General Medicine·Mohsen AghaeiEmad Babakhanzadeh
Jun 24, 2020·Biomolecules·Nina Criado SantosPaula Nunes-Hasler
Nov 13, 2020·Cell Calcium·Giovanni MonacoStephen B Ting
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Chenlu LiHaijia Yu
Mar 20, 2021·Frontiers in Cell and Developmental Biology·Ulises Ahumada-CastroCésar Cárdenas
Sep 1, 2021·Cell Death & Disease·Yanyan CaoLei Liu

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