ホスファチジルイノシトールリン脂質の可視化動態分析

抄録

Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P₃) regulates diverse cellular functions including cell proliferation and apoptosis, and is related to diabetes, cancer, etc.; however, little is known about exactly when, where and how PtdIns(3,4,5)P₃ is produced. We have developed fluorescent indicators for PtdIns(3,4,5)P₃ to reveal spatio-temporal regulations of PtdIns(3,4,5)P₃ production in single living cells. After ligand stimulations, PtdIns(3,4,5)P₃ levels increased to a larger extent at the endomembranes, i.e. the ER and Golgi, than at the plasma membrane. This PtdIns(3,4,5)P₃ increase at the endomembranes was found to originate from its in situ production at the endomembranes, a process stimulated directly by receptor tyrosine kinases endocytosed from the plasma membrane to the endomembranes. The demonstration of PtdIns(3,4,5)P₃ production through receptor endocytosis addresses a long-lasting question about how downstream signaling pathways including Akt are activated at intracellular compartments remote from the plasma membrane. [J Physiol Sci. 2006;56 Suppl:S8]