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

Cell Calcium. 2018 Jun;72:62-69. Epub 2018 Mar 13
Ilari Pulli 1 , Taru Lassila 1 , Guoping Pan 2 , Daoguang Yan 2 , Vesa M Olkkonen 3 , Kid Törnquist 4
Ilari Pulli 1 , Taru Lassila 1 , Guoping Pan 2 , Daoguang Yan 2 , Vesa M Olkkonen 3 , Kid Törnquist 4
+ et al

[No authors listed]

Author information
  • 1 Åbo Akademi University, Tykistökatu 6A, 20520 Turku, Finland.
  • 2 The Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
  • 3 Minerva Foundation Institute For Medical Research, Biomedicum Helsinki, 00290 Helsinki, Finland; Department of Anatomy, Faculty of Medicine, FI-00014 University of Helsinki, Finland.
  • 4 Åbo Akademi University, Tykistökatu 6A, 20520 Turku, Finland; Minerva Foundation Institute For Medical Research, Biomedicum Helsinki, 00290 Helsinki, Finland. Electronic address: ktornqvi@abo.fi.

摘要


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.

KEYWORDS: Calcium, Caveolae, Endoplasmic reticulum, Mitochondria, ORP5, ORP8