Control of the signaling role of PtdIns(4)P at the plasma membrane through H2O2-dependent inactivation of synaptojanin 2 during endocytosis
Su In Jo,
Suree Kim,
Jung Mi Lim,
Sue Goo Rhee,
Bo-Gyeong Jeong,
Sun-Shin Cha,
Jae-Byum Chang,
Dongmin Kang
Affiliations
Su In Jo
Department of Life Science, Ewha Womans University, Seoul, Republic of Korea
Suree Kim
Fluorescence Core Imaging Center and Bioimaging Data Curation Center, Ewha Womans University, Seoul, Republic of Korea
Jung Mi Lim
Biochemistry and Biophysics Center, NHLBI, National Institutes of Health, Bethesda, MD, 20892, USA
Sue Goo Rhee
Biochemistry and Biophysics Center, NHLBI, National Institutes of Health, Bethesda, MD, 20892, USA
Bo-Gyeong Jeong
R&D Division, TODD PHARM CO. LTD., Seoul, Republic of Korea
Sun-Shin Cha
R&D Division, TODD PHARM CO. LTD., Seoul, Republic of Korea; Department of Chemistry & Nanoscience, Ewha Womans University, Seoul, Republic of Korea
Jae-Byum Chang
Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
Dongmin Kang
Department of Life Science, Ewha Womans University, Seoul, Republic of Korea; Fluorescence Core Imaging Center and Bioimaging Data Curation Center, Ewha Womans University, Seoul, Republic of Korea; Corresponding author. Department of Life Science, Ewha Womans University, Seoul, Republic of Korea.
Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] is implicated in various processes, including hormone-induced signal transduction, endocytosis, and exocytosis in the plasma membrane. However, how H2O2 accumulation regulates the levels of PtdIns(4,5)P2 in the plasma membrane in cells stimulated with epidermal growth factors (EGFs) is not known. We show that a plasma membrane PtdIns(4,5)P2-degrading enzyme, synaptojanin (Synj) phosphatase, is inactivated through oxidation by H2O2. Intriguingly, H2O2 inhibits the 4-phosphatase activity of Synj but not the 5-phosphatase activity. In EGF-activated cells, the oxidation of Synj dual phosphatase is required for the transient increase in the plasma membrane levels of phosphatidylinositol 4-phosphate [PtdIns(4)P], which can control EGF receptor-mediated endocytosis. These results indicate that intracellular H2O2 molecules act as signaling mediators to fine-tune endocytosis by controlling the stability of plasma membrane PtdIns(4)P, an intermediate product of Synj phosphoinositide dual phosphatase.
