田邊 賢司
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Associate Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Nanoscale analysis reveals agonist-sensitive and heterogeneous pools of phosphatidylinositol 4-phosphate in the plasma membrane.
Journal Formal name:Biochimica et biophysica acta
Abbreviation:Biochim Biophys Acta
ISSN code:(0006-3002)0006-3002(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 1858(6),pp.1298-1305
Author and coauthor Yoshida Akane, Shigekuni Mikiko, Tanabe Kenji, Fujita Akikazu
Publication date 2016/06
Summary Phosphatidylinositol 4-phosphate [PtdIns(4)P] is the immediate precursor of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], which is localized to the cytoplasmic leaflet of the plasma membrane and has been reported to possess multiple cell biological functions. Direct evidence showing the distribution of PtdIns(4)P pools at a nanoscale when the plasma membrane PtdIns(4,5)P2 is hydrolyzed by agonist stimulation is lacking. To analyze the distribution of PtdIns(4)P at a nanoscale, we employed an electron microscopy technique that specifically labels PtdIns(4)P on the freeze-fracture replica of the plasma membrane. This method minimizes the possibility of artificial perturbation, because molecules in the membrane are physically immobilized in situ. Using this technique, we observed no PtdIns(4)P in the caveolae of normal cultured human fibroblasts, although PtdIns(4,5)P2 has been shown to be highly concentrated in them in our previous report. When cells were stimulated with angiotensin II, the level of PtdIns(4)P in the undifferentiated membrane transiently decreased to 64.3% at 10s, began to increase at 30s and largely increased to 341.9% at 40s, and then returned to the initial level at 130s after the stimulation. Interestingly, PtdIns(4)P localized at the caveolae at 70 and 130s after the stimulation. These results suggest that the level of the PtdIns(4)P pool in the plasma membrane is sensitive and the distribution of PtdIns(4)P dramatically changes by agonist stimulation, and there are active sites of production or replenishment of PtdIns(4)P at undifferentiated membrane and caveolar areas.
DOI 10.1016/j.bbamem.2016.03.011
PMID 26972044