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• W2948060103 abstract "Abstract The formation and disruption of synaptic connections during development is a fundamental step in neural circuit formation. Subneuronal structures such as neurites are known to be sensitive to the level of spontaneous neuronal activity but the specifics of how neurotransmitter-induced calcium activity regulates neurite homeostasis are not yet fully understood. In response to stimulation by neurotransmitters such as acetylcholine, calcium responses in cells are mediated the Gαq/phospholipase Cβ (PLCβ)/ phosphatidylinositol 4,5 bisphosphate (PI(4, 5)P 2 ) signaling pathway. Here, we show that prolonged Gαq stimulation results in the retraction of neurites in PC12 cells and rupture of neuronal synapses by modulating membrane tension. To understand the underlying cause, we dissected the behavior of individual components of the Gαq/PLCβ/PI(4, 5)P 2 pathway during retraction, and correlated these to the retraction of the membrane and cytoskeletal elements impacted by calcium signaling. We developed a mathematical model that combines biochemical signaling with membrane tension and cytoskeletal mechanics, to show how signaling events are coupled to retraction velocity, membrane tension and actin dynamics. The coupling between calcium and neurite retraction is shown to be operative in the C. elegans nervous system. This study uncovers a novel mechanochemical connection between the Gαq/PLCβ/(PI(4, 5)P 2 pathway that couples calcium responses with neural plasticity." @default.
• W2948060103 created "2019-06-14" @default.
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• W2948060103 date "2019-06-06" @default.
• W2948060103 modified "2023-10-16" @default.
• W2948060103 title "Gq-mediated calcium dynamics and membrane tension modulate neurite plasticity" @default.
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• W2948060103 doi "https://doi.org/10.1101/661975" @default.
• W2948060103 hasPublicationYear "2019" @default.
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