The study investigates the regulatory mechanisms of non-lethal caspase activation in the nervous system. The authors found that the executioner caspase Drice is primarily localized to the cell membrane in the adult Drosophila brain, in proximity to a specific isoform of the cell adhesion molecule Fasciclin 3 (Fas3G).
To study the role of Fas3G in caspase regulation, the authors developed a novel reporter system called MASCaT, which enables highly sensitive detection of non-lethal caspase activity in a cell-type-specific manner. Using MASCaT, they demonstrated that overexpression of Fas3G enhances non-lethal caspase activation in olfactory receptor neurons (ORNs) without inducing cell death.
Mechanistically, Fas3G overexpression increases the expression of the initiator caspase Dronc, which also comes in close proximity to Fas3G. The Dronc-dependent non-lethal caspase activation facilitated by Fas3G overexpression suppresses innate olfactory attraction behavior in flies.
The findings suggest that the subcellular localization of executioner caspases, defined by their proximal proteins, is a key mechanism regulating non-lethal caspase activation. Modulating the proximity of caspases to specific membrane proteins provides a means to reversibly control neuronal function without inducing cell death.
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by Muramoto,M.,... : www.biorxiv.org 07-20-2023
https://www.biorxiv.org/content/10.1101/2023.07.20.549821v3Mélyebb kérdések