
Subcellularly restricted non-lethal caspase activation is regulated by the proximity of executioner caspases to specific membrane proteins, such as the Fasciclin 3 isoform G, which promotes the expression and recruitment of the initiator caspase Dronc.


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The nervous system undergoes functional modification independent on cell turn over. Caspase participates in reversible neuronal modulation via non-lethal activation. However, the mechanism that enables non-lethal activation remains unclear. Here, we analyzed proximal proteins of Drosophila executioner caspase in the adult brain using TurboID. We discovered that executioner caspase Drice is, as an inactive proform, proximal to cell membrane proteins, including a specific splicing isoform of cell adhesion molecule Fasciclin 3 (Fas3), Fas3G. To investigate whether sequestration of executioner caspase to plasma membrane of axons is the mechanism for non-lethal activation, we developed a Gal4-Manipulated Area-Specific CaspaseTracker/CasExpress system for sensitive monitoring of caspase activity near plasma membrane. We demonstrated that Fas3G -overexpression promotes caspase activation in olfactory receptor neurons without killing them, by inducing expression of initiator caspase Dronc, which also comes close to Fas3G. Physiologically, Fas3G -overexpression facilitated non-lethal activation suppresses innate olfactory attraction behavior. Our findings suggest that subcellularly-restricted caspase activation, defined by caspase proximal proteins, is the mechanism for non-lethal activation, opening the methodological development of reversible modification of neuronal function via regulating caspase proximal proteins.

### Competing Interest Statement

The authors have declared no competing interest.

Executioner caspase is proximal to Fasciclin 3 which facilitates non-lethal activation in Drosophila olfactory receptor neurons

proximity-based-regulation-of-non-lethal-caspase-activation-in-drosophila-olfactory-receptor-neurons


Proximity-Based Regulation of Non-Lethal Caspase Activation in Drosophila Olfactory Receptor Neurons
