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

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http://hdl.handle.net/10138/303650

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Pulli , I , Lassila , T , Pan , G , Yan , D , Olkkonen , V M & Törnquist , K 2018 , ' Oxysterol-binding protein related-proteins (ORPs) 5 and 8 regulate calcium signaling at specific cell compartments ' , Cell Calcium , vol. 72 , pp. 62-69 . https://doi.org/10.1016/j.ceca.2018.03.001

Title: Oxysterol-binding protein related-proteins (ORPs) 5 and 8 regulate calcium signaling at specific cell compartments
Author: Pulli, Ilari; Lassila, Taru; Pan, Guoping; Yan, Daoguang; Olkkonen, Vesa M.; Törnquist, Kid
Contributor: University of Helsinki, Medicum
Date: 2018-06
Language: eng
Number of pages: 8
Belongs to series: Cell Calcium
ISSN: 0143-4160
URI: http://hdl.handle.net/10138/303650
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 cell proliferation. Our results show that ORP5/8 regulate Ca2+ signaling at specific MCS foci. These local ORP5/8-mediated Ca2+ signaling events are likely to play roles in processes such as mitochondrial respiration and cell proliferation.
Subject: 3111 Biomedicine
1182 Biochemistry, cell and molecular biology
ORP5
ORP8
Caveolae
Mitochondria
Endoplasmic reticulum
Calcium
SURVIVAL
UNIPORTER
ACTIVATION
MITOCHONDRIA
FAS-MEDIATED APOPTOSIS
SENSORS
TRANSPORT
MEMBRANE CONTACT SITES
ENDOPLASMIC-RETICULUM
CAVEOLAE
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