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G?q-mediated calcium dynamics and membrane tension modulate neurite plasticity.

ABSTRACT: The formation and disruption of synaptic connections during development are 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 by the G?q/phospholipase C? (PLC?)/phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) signaling pathway. Here, we show that prolonged G?q stimulation results in the retraction of neurites in PC12 cells and the rupture of neuronal synapses by modulating membrane tension. To understand the underlying cause, we dissected the behavior of individual components of the G?q/PLC?/PI(4,5)P₂ pathway during retraction and correlated these with 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 Caenorhabditis elegans nervous system. This study uncovers a novel mechanochemical connection between G?q/PLC? /PI(4,5)P₂ that couples calcium responses with neural plasticity.

SUBMITTER: Pearce KM

PROVIDER: S-EPMC7202066 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Gαq-mediated calcium dynamics and membrane tension modulate neurite plasticity.

Pearce Katherine M KM Bell Miriam M Linthicum Will H WH Wen Qi Q Srinivasan Jagan J Rangamani Padmini P Scarlata Suzanne S

Molecular biology of the cell 20191211 7

The formation and disruption of synaptic connections during development are 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 by the Gαq/phospholipase ...[more]

PMID: 31825720

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Dataset Information

G?q-mediated calcium dynamics and membrane tension modulate neurite plasticity.

Publications

Gαq-mediated calcium dynamics and membrane tension modulate neurite plasticity.

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