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
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	Phospholipase C-β1 and β4 contribute to non-genetic cell-to-cell variability in histamine-induced calcium signals in HeLa cells
掲載誌名	正式名：PLOS ONE 略　 称：PLOS ONE ISSNコード：19326203
掲載区分	国外
巻・号・頁	9(1),pp.e86410
著者・共著者	Sachiko Ishida, Toru Matsu-ura, Kiyoko Fukami, Takayuki Michikawa, Katsuhiko Mikoshiba
担当区分	2nd著者
発行年月	2014/01
概要	A uniform extracellular stimulus triggers cell-specific patterns of Ca(2+) signals, even in genetically identical cell populations. However, the underlying mechanism that generates the cell-to-cell variability remains unknown. We monitored cytosolic inositol 1,4,5-trisphosphate (IP3) concentration changes using a fluorescent IP3 sensor in single HeLa cells showing different patterns of histamine-induced Ca(2+) oscillations in terms of the time constant of Ca(2+) spike amplitude decay and the Ca(2+) oscillation frequency. HeLa cells stimulated with histamine exhibited a considerable variation in the temporal pattern of Ca(2+) signals and we found that there were cell-specific IP3 dynamics depending on the patterns of Ca(2+) signals. RT-PCR and western blot analyses showed that phospholipase C (PLC)-β1, -β3, -β4, -γ1, -δ3 and -ε were expressed at relatively high levels in HeLa cells. Small interfering RNA-mediated silencing of PLC isozymes revealed that PLC-β1 and PLC-β4 were specifically involved in the histamine-induced IP3 increases in HeLa cells. Modulation of IP3 dynamics by knockdown or overexpression of the isozymes PLC-β1 and PLC-β4 resulted in specific changes in the characteristics of Ca(2+) oscillations, such as the time constant of the temporal changes in the Ca(2+) spike amplitude and the Ca(2+) oscillation frequency, within the range of the cell-to-cell variability found in wild-type cell populations. These findings indicate that the heterogeneity in the process of IP3 production, rather than IP3-induced Ca(2+) release, can cause cell-to-cell variability in the patterns of Ca(2+) signals and that PLC-β1 and PLC-β4 contribute to generate cell-specific Ca(2+) signals evoked by G protein-coupled receptor stimulation.