@article{9080c56ac24d4394bbf74a69d10682c0,
title = "Characterization of α-synuclein N-terminal domain as a novel cellular phosphatidic acid sensor",
abstract = "Tracking the localization and dynamics of the intracellular bioactive lipid phosphatidic acid (PA) is important for understanding diverse biological phenomena. Although several PA sensors have been developed, better ones are still needed for comprehensive PA detection in cells. We recently found that α-synuclein (α-Syn) selectively and strongly bound to PA in vitro. Here, we revealed that the N-terminal region of α-Syn (α-Syn-N) specifically bound to PA, with a dissociation constant of 6.6 μm. α-Syn-N colocalized with PA-producing enzymes, diacylglycerol kinase (DGK) β at the plasma membrane (PM), myristoylated DGKζ at the Golgi apparatus, phorbol ester-stimulated DGKγ at the PM, and phospholipase D2 at the PM and Golgi but not with the phosphatidylinositol-4,5-bisphosphate-producing enzyme in COS-7 cells. However, α-Syn-N failed to colocalize with them in the presence of their inhibitors and/or their inactive mutants. These results indicate that α-Syn-N specifically binds to cellular PA and can be applied as an excellent PA sensor.",
author = "Haruka Yamada and Satoru Mizuno and Shotaro Honda and Daisuke Takahashi and Fumio Sakane",
note = "Funding Information: We acknowledge Ono Pharmaceutical Co., Ltd. for kindly providing Compound A. This work was supported in part by grants from MEXT/JSPS (KAKENHI Grant Numbers: 26291017 (Grant‐in‐Aid for Scientific Research (B)), 15K14470 (Grant‐in‐Aid for Challenging Exploratory Research), and 17H03650 (Grant‐in‐Aid for Scientific Research (B)); the Futaba Electronic Memorial Foundation; the Ono Medical Research Foundation; the Japan Foundation for Applied Enzymology; the Food Science Institute Foundation; the Skylark Food Science Institute; the Asahi Group Foundation; the Japan Milk Academic Alliance; the Japan Food Chemical Research Foundation; and the SENSHIN Medical Research Foundation (FS). Funding Information: FS received funding from Ono Pharmaceutical Co., Ltd. All remaining authors declare no conflict of interest. Funding Information: We acknowledge Ono Pharmaceutical Co., Ltd. for kindly providing Compound A. This work was supported in part by grants from MEXT/JSPS (KAKENHI Grant Numbers: 26291017 (Grant-in-Aid for Scientific Research (B)), 15K14470 (Grant-in-Aid for Challenging Exploratory Research), and 17H03650 (Grant-in-Aid for Scientific Research (B)); the Futaba Electronic Memorial Foundation; the Ono Medical Research Foundation; the Japan Foundation for Applied Enzymology; the Food Science Institute Foundation; the Skylark Food Science Institute; the Asahi Group Foundation; the Japan Milk Academic Alliance; the Japan Food Chemical Research Foundation; and the SENSHIN Medical Research Foundation (FS). Publisher Copyright: {\textcopyright} 2019 Federation of European Biochemical Societies",
year = "2020",
month = jun,
day = "1",
doi = "10.1111/febs.15137",
language = "English",
volume = "287",
pages = "2212--2234",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "11",
}