구.추천논문
- 조회1,386
Mira Sohn1, Marek Korzeniowski1, James P. Zewe2, Rachel C. Wills2, Gerald R.V. Hammond2, Jana Humpolickova3, Lukas Vrzal3, Dominika Chalupska3, Vaclav Veverka3, Gregory D. Fairn4, Evzen Boura3, and Tamas Balla1,*
1Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; 2Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA; 3Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic; 4Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
*Correspondence to Tamas 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.
논문정보
- Research article
- 2018년 02월 (BRIC 등록일 2020-07-23)
- 국외 연구진
- 구・추천논문
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