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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 |
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URN: | urn:nbn:de:hebis:30:3-508542 |
DOI: | https://doi.org/10.1016/j.molcel.2019.06.037 |
ISSN: | 1097-4164 |
ISSN: | 1097-2765 |
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 |
Language: | English |
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 |
Volume: | 75 |
Issue: | 5 |
Page Number: | 24 |
First Page: | 1043 |
Last Page: | 1057.e8 |
Note: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
HeBIS-PPN: | 454015046 |
Institutes: | Physik / Physik |
Angeschlossene und kooperierende Institutionen / MPI für Biophysik | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |