Characterization of α-synuclein N-terminal domain as a novel cellular phosphatidic acid sensor

Haruka Yamada, Satoru Mizuno, Shotaro Honda, Daisuke Takahashi, Fumio Sakane

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2212-2234
Number of pages23
JournalFEBS Journal
Issue number11
Publication statusPublished - Jun 1 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Characterization of α-synuclein N-terminal domain as a novel cellular phosphatidic acid sensor'. Together they form a unique fingerprint.

Cite this