Open AccessORP3 phosphorylation regulates phosphatidylinositol 4-phosphate and Ca2+ dynamics at PM-ER contact sites
Author(s) -
Gergő Gulyás,
Minji Sohn,
Yeun Ju Kim,
Péter Várnai,
Tamás Balla
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.237388
Subject(s) - biology , phosphatidylinositol , phosphatidic acid , microbiology and biotechnology , plant lipid transfer proteins , phosphorylation , membrane contact site , organelle , biochemistry , membrane , membrane protein , phospholipid , integral membrane protein , gene
Oxysterol-binding protein (OSBP)-related proteins (ORPs) mediate non-vesicular lipid-transfer between intracellular membranes. Phosphoinositide gradients play important roles in the ability of OSBP and some ORPs to transfer cholesterol and phosphatidylserine between the ER and other organelle membranes. Here we show that PM association of ORP3, a less characterized ORP family member, is triggered by PKC activation, especially when combined with Ca2+ increases and is determined by both PI(4,5)P2 and PI4P. After activation, ORP3 efficiently extracts PI4P and to a small extent phosphatidic acid from the PM and slightly increases PM cholesterol levels. Full activation of ORP3 results in decreased PM PI4P levels and inhibits Ca2+ entry via the store-operated Ca2+ entry pathway. The C-terminal region of ORP3 that follows the strictly defined lipid transfer domain, is found to be critical for the proper localization and function of the protein.