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Nat Chem Biol. 2016 Mar;12(3):159-66. doi: 10.1038/nchembio.2000. Epub 2016 Jan 11.

Frequency and amplitude control of cortical oscillations by phosphoinositide waves.

Xiong D1,2,3, Xiao S2,3, Guo S2,3, Lin Q2, Nakatsu F4, Wu M1,2,3.

Author information

1
Mechanobiology Institute, National University of Singapore, Singapore.
2
Department of Biological Sciences, National University of Singapore, Singapore.
3
Centre for Bioimaging Sciences, National University of Singapore, Singapore.
4
Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Abstract

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)P2 regulate the amplitude of cyclic membrane waves while PtdIns(3,4)P2 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.

PMID:
26751515
DOI:
10.1038/nchembio.2000
[Indexed for MEDLINE]

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