PT  - JOURNAL ARTICLE
AU  - Katherine M. Pearce
AU  - Miriam Bell
AU  - Will H. Linthicum
AU  - Qi Wen
AU  - Jagan Srinivasan
AU  - Padmini Rangamani
AU  - Suzanne Scarlata
TI  - Decoding the Mechanochemistry of Neurite Plasticity
AID  - 10.1101/661975
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 661975
4099  - http://biorxiv.org/content/early/2019/06/06/661975.short
4100  - http://biorxiv.org/content/early/2019/06/06/661975.full
AB  - Normal calcium responses to hormones and neurotransmitters are critical for neuronal health. Calcium responses are carried out by the Gαq/phospholipase Cβ (PLCβ)/phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) signaling pathway. Here, we show that Gαq stimulation results in the retraction of neurites in PC12 cells and rupture of neuronal synapses. 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 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)P2 pathway that couples calcium responses with neural plasticity.