期刊
NATURE CHEMICAL BIOLOGY
卷 12, 期 3, 页码 159-166出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2000
关键词
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资金
- National Research Foundation (NRF) Singapore under its NRF Fellowship Program [NRF-NRFF2011-09]
- Mechanobiology Institute at National University of Singapore
Rhythmicity is prevalent in the cortical dynamics of diverse single and multicellular systems. Current models of cortical oscillations focus primarily on cytoskeleton-based feedbacks, but information on signals upstream of the actin cytoskeleton is limited. In addition, inhibitory mechanisms-especially local inhibitory mechanisms, which ensure proper spatial and kinetic controls of activation-are not well understood. Here, we identified two phosphoinositide phosphatases, synaptojanin 2 and SHIP1, that function in periodic traveling waves of rat basophilic leukemia (RBL) mast cells. The local, phase-shifted activation of lipid phosphatases generates sequential waves of phosphoinositides. By acutely perturbing phosphoinositide composition using optogenetic methods, we showed that pulses of PtdIns(4,5)P-2 regulate the amplitude of cyclic membrane waves while PtdIns(3,4)P-2 sets the frequency. Collectively, these data suggest that the spatiotemporal dynamics of lipid metabolism have a key role in governing cortical oscillations and reveal how phosphatidylinositol 3-kinases (PI3K) activity could be frequency encoded by a phosphatase-dependent inhibitory reaction.
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