Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

被引:61
|
作者
Wen, Peter J. [1 ,2 ]
Osborne, Shona L. [1 ,2 ]
Zanin, Mark [3 ]
Low, Pei Ching [1 ,2 ]
Wang, Hai-Tao A. [1 ,2 ]
Schoenwaelder, Simone M. [4 ]
Jackson, Shaun P. [4 ]
Wedlich-Soeldner, Roland [5 ]
Vanhaesebroeck, Bart [6 ]
Keating, Damien J. [3 ]
Meunier, Frederic A. [1 ,2 ]
机构
[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia
[2] Sch Biomed Sci, Brisbane, Qld 4072, Australia
[3] Flinders Univ S Australia, Dept Human Physiol, Adelaide, SA 5001, Australia
[4] Monash Univ, Australian Ctr Blood Dis, Melbourne, Vic 3004, Australia
[5] Max Planck Inst Biochem, Res Grp Cellular Dynam & Cell Patterning, D-82152 Martinsried, Germany
[6] Queen Mary Univ London, Ctr Cell Signalling, Barts Canc Inst, London EC1M 6BQ, England
来源
NATURE COMMUNICATIONS | 2011年 / 2卷
基金
英国医学研究理事会;
关键词
REGULATED EXOCYTOSIS; NEUROENDOCRINE CELLS; PHOSPHOLIPASE-C; PI; 3-KINASE; PTEN; GRANULES; PROTEIN; POLYMERIZATION; ACTIVATION; MECHANISM;
D O I
10.1038/ncomms1500
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Neurosecretory vesicles undergo docking and priming before Ca(2+)-dependent fusion with the plasma membrane. Although de novo synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P(2)) is required for exocytosis, its precise contribution is still unclear. Here we show that inhibition of the p110 delta isoform of PI3-kinase by IC87114 promotes a transient increase in PtdIns(4,5)P(2), leading to a potentiation of exocytosis in chromaffin cells. We then exploit this pathway to examine the effect of a transient PtdIns(4,5)P(2) increase on neurosecretory vesicles behaviour, outside the context of a secretagogue stimulation. Our results demonstrate that a rise in PtdIns(4,5)P(2) is sufficient to promote the mobilization and recruitment of secretory vesicles to the plasma membrane via Cdc42-mediated actin reorganization. PtdIns(4,5)P(2), therefore, orchestrates the actin-based conveyance of secretory vesicles to the plasma membrane.
引用
收藏
页数:11
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