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  Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis

Nishimura, T., Gecht, M., Covino, R., Hummer, G., Surma, M. A., Klose, C., et al. (2019). Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis. Molecular Cell, 75(5), 1043-1057. doi:10.1016/j.molcel.2019.06.037.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-7A5A-F Version Permalink: http://hdl.handle.net/21.11116/0000-0004-AA3F-7
Genre: Journal Article

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 Creators:
Nishimura, Taki1, Author
Gecht, Michael2, Author              
Covino, Roberto2, Author              
Hummer, Gerhard2, 3, Author              
Surma, Michal A.4, Author
Klose, Christian4, Author
Arai, Hiroyuki5, 6, Author
Kono, Nozomu5, 7, Author
Stefan, Christopher J.1, Author
Affiliations:
1MRC Laboratory for Molecular Cell Biology, University College London, London, UK, ou_persistent22              
2Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
3Institute for Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany, ou_persistent22              
4Lipotype GmbH, Dresden, Germany, ou_persistent22              
5Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan, ou_persistent22              
6AMED-CREST, Japan Agency for Medical Research and Development, Otemachi, Chiyodaku, Tokyo, Japan, ou_persistent22              
7PRIME, Japan Agency for Medical Research and Development, Otemachi, Chiyodaku, Tokyo, Japan, ou_persistent22              

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Free keywords: endoplasmic reticulum; oxysterol-binding protein homology protein; phosphatidylinositol 4-phosphate 5-kinase; phosphatidylserine; plasma membrane; sterol; unsaturated phospholipid
 Abstract: 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.

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Language(s): eng - English
 Dates: 2019-05-132019-01-082019-06-252019-08-082019-09-05
 Publication Status: Published in print
 Pages: 24
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.molcel.2019.06.037
 Degree: -

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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 75 (5) Sequence Number: - Start / End Page: 1043 - 1057 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929