Osh proteins control nanoscale lipid organization necessary for PI(4,5)P2 synthesis

  • The plasma membrane (PM) is composed of a complex lipid mixture that forms heterogeneous membrane environments. Yet, how small-scale lipid organization controls physiological events at the PM remains largely unknown. Here, we show that ORP-related Osh lipid exchange proteins are critical for the synthesis of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2], a key regulator of dynamic events at the PM. In real-time assays, we find that unsaturated phosphatidylserine (PS) and sterols, both Osh protein ligands, synergistically stimulate phosphatidylinositol 4-phosphate 5-kinase (PIP5K) activity. Biophysical FRET analyses suggest an unconventional co-distribution of unsaturated PS and phosphatidylinositol 4-phosphate (PI4P) species in sterol-containing membrane bilayers. Moreover, using in vivo imaging approaches and molecular dynamics simulations, we show that Osh protein-mediated unsaturated PI4P and PS membrane lipid organization is sensed by the PIP5K specificity loop. Thus, ORP family members create a nanoscale membrane lipid environment that drives PIP5K activity and PI(4,5)P2 synthesis that ultimately controls global PM organization and dynamics.
Author:Taki NishimuraORCiD, Michael GechtORCiDGND, Roberto CovinoORCiD, Gerhard HummerORCiD, Michał Surma, Christian Klose, Hiroyuki Arai, Nozomu Kono, Christopher J. Stefan
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31402097
Parent Title (English):Molecular cell
Publisher:Cell Press ; Elsevier
Place of publication:[Cambridge, Mass.] ; New York, NY
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/08/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/09/12
Tag:endoplasmic reticulum; oxysterol-binding protein homology protein; phosphatidylinositol 4-phosphate 5-kinase; phosphatidylserine; plasma membrane; sterol; unsaturated phospholipid
Page Number:24
First Page:1043
Last Page:1057.e8
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Institutes:Physik / Physik
Angeschlossene und kooperierende Institutionen / MPI für Biophysik
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik
Licence (German):License LogoCreative Commons - Namensnennung 4.0