한빛사논문
- 조회390
Yeun Ju Kim1, Joshua G Pemberton1, Andrea Eisenreichova2, Amrita Mandal1, Alena Koukalova1, Pooja Rohilla1, Mira Sohn1, Andrei W Konradi3, Tracy T Tang3, Evzen Boura2 & Tamas Balla1
1Section on Molecular Signal Transduction, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD20892, USA.
2Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nam. 2., 166 10 Prague 6, Czech Republic.
3Vivace Therapeutics,San Mateo, CA 94404, USA.
Corresponding author : Tamas Balla
Abstract
Phosphatidylinositol (PI) is the precursor lipid for the minor phosphoinositides (PPIns), which are critical for multiple functions in all eukaryotic cells. It is poorly understood how phosphatidylinositol, which is synthesized in the ER, reaches those membranes where PPIns are formed. Here, we used VT01454, a recently identified inhibitor of class I PI transfer proteins (PITPs), to unravel their roles in lipid metabolism, and solved the structure of inhibitor-bound PITPNA to gain insight into the mode of inhibition. We found that class I PITPs not only distribute PI for PPIns production in various organelles such as the plasma membrane (PM) and late endosomes/lysosomes, but that their inhibition also significantly reduced the levels of phosphatidylserine, di- and triacylglycerols, and other lipids, and caused prominent increases in phosphatidic acid. While VT01454 did not inhibit Golgi PI4P formation nor reduce resting PM PI(4,5)P2 levels, the recovery of the PM pool of PI(4,5)P2 after receptor-mediated hydrolysis required both class I and class II PITPs. Overall, these studies show that class I PITPs differentially regulate phosphoinositide pools and affect the overall cellular lipid landscape.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-18)
- 국외 연구진
- 생명과학 > 세포생물학
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