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 Gαq/phospholipase Cβ (PLCβ)/phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) signaling pathway. Here, we show that prolonged Gαq 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 Gαq/PLCβ/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 Gαq/PLCβ /PI(4,5)P2 that couples calcium responses with neural plasticity.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Pearce KM,Bell M,Linthicum WH,Wen Q,Srinivasan J,Rangamani P,Scarlata Sdoi
10.1091/mbc.E19-09-0536subject
Has Abstractpub_date
2020-03-19 00:00:00pages
683-694issue
7eissn
1059-1524issn
1939-4586journal_volume
31pub_type
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