PI(4,5)P2 controls plasma membrane PI4P and PS levels via ORP5/8 recruitment to ER-PM contact sites

The Journal of Cell Biology
Mira SohnTamas Balla

Abstract

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a critically important regulatory lipid of the plasma membrane (PM); however, little is known about how cells regulate PM PI(4,5)P2 levels. Here, we show that the phosphatidylinositol 4-phosphate (PI4P)/phosphatidylserine (PS) transfer activity of the endoplasmic reticulum (ER)-resident ORP5 and ORP8 is regulated by both PM PI4P and PI(4,5)P2 Dynamic control of ORP5/8 recruitment to the PM occurs through interactions with the N-terminal Pleckstrin homology domains and adjacent basic residues of ORP5/8 with both PI4P and PI(4,5)P2 Although ORP5 activity requires normal levels of these inositides, ORP8 is called on only when PI(4,5)P2 levels are increased. Regulation of the ORP5/8 attachment to the PM by both phosphoinositides provides a powerful means to determine the relative flux of PI4P toward the ER for PS transport and Sac1-mediated dephosphorylation and PIP 5-kinase-mediated conversion to PI(4,5)P2 Using this rheostat, cells can maintain PI(4,5)P2 levels by adjusting the availability of PI4P in the PM.

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Citations

Jun 29, 2018·Molecular Biology of the Cell·Rachel C WillsGerald R V Hammond
Jul 25, 2019·Journal of Cell Science·Taylor E MillerKwang-Jin Cho
Oct 28, 2019·The Journal of Cell Biology·Ximing DuHongyuan Yang
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Datasets Mentioned

BETA
BC111728
AF048695

Methods Mentioned

BETA
confocal microscopy
BRET
NMR
confocal
transfection
PCR
size exclusion chromatography
Fluorescence

Software Mentioned

OdysseyV3
Zen
GraphPad Prism
Adobe Photoshop
BRET

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