マツウラ　トオル   MATSUURA TORU   松浦　徹    所属   関西医科大学  病理学講座    職種   講師
言語種別	英語
発表タイトル	A new metabolic pathway of phosphoinositides
会議名	第43回日本分子生物学会年会
学会区分	全国規模の学会
招聘	招聘
発表形式	口頭
講演区分	シンポジウム・ワークショップ パネル（公募）
発表者・共同発表者	松浦徹
発表年月日	2020/12/04
開催地 （都市, 国名）	Web開催
概要	Phosphoinositides (PIs) are lipid second messengers that regulate many cell functions and their dysregulation causes diseases such as cancer and developmental disorders. Eight species of PIs form a circuit, which starts from phosphatidylinositol and is fluxed to the subsequent PIs by sequential phosphorylation and dephosphorylation of its inositol head group. Accumulating evidence indicates that conversions of certain PIs are unidirectional in vivo, which could potentially provide the directional flow in the network. However, overall mass flux in the phosphoinositide circuit remains unknown because tracer analysis of phosphoinositide flux has been challenging. Here, we developed a kinetic model and discovered a homeostatic PI current under steady state conditions. Our model showed a GTP sensor protein, phosphatidylinositol-5-phosphate-4-kinase (PI5P4K), works as one of the major enzymes to produce the PI current. Surprisingly, model predictions and knock-out experiments of PI5P4K revealed a new metabolic pathway of PIs is necessary to maintain the PI current.