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


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.

SUBMITTER: Sohn M 

PROVIDER: S-EPMC5940310 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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PI(4,5)P<sub>2</sub> controls plasma membrane PI4P and PS levels via ORP5/8 recruitment to ER-PM contact sites.

Sohn Mira M   Korzeniowski Marek M   Zewe James P JP   Wills Rachel C RC   Hammond Gerald R V GRV   Humpolickova Jana J   Vrzal Lukas L   Chalupska Dominika D   Veverka Vaclav V   Fairn Gregory D GD   Boura Evzen E   Balla Tamas T  

The Journal of cell biology 20180222 5


Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P<sub>2</sub>) is a critically important regulatory lipid of the plasma membrane (PM); however, little is known about how cells regulate PM PI(4,5)P<sub>2</sub> 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)P<sub>2</sub> Dynamic control of ORP5/8 recruitment to the PM occurs through intera  ...[more]

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