Brain of an adult fruit fly showing caspase (magenta), its nearby protein Fas3G (green), and nuclei (blue). Image credit: Natsuki Shinoda (CC BY 4.0)
Networks of neurons in the nervous system are continuously adapting and changing their role, often without having to kill and replace cells. A group of enzymes called caspases – which are best known for initiating cell death – are thought to play a significant role in this process.
Studies have shown that caspases contribute to shaping neural connections and are involved in brain functions such as learning and memory. However, it remains unclear how the enzymes safely perform these tasks without mistakenly killing neurons.
To investigate this question, Muramoto, Hanawa et al. employed a technique called TurboID to label caspases and their nearby proteins in the brains of fruit flies. Their analysis showed that caspases are typically located close to proteins in the membrane that surrounds the interior of a cell.
Muramoto, Hanawa et al. then increased the production of one of these membrane proteins, called Fas3G, in olfactory neurons which are responsible for detecting smells. This increased the activity of caspases without triggering cell death. It also reduced how attracted the flies were to odors they are normally drawn to, suggesting that non-lethal caspase activation can suppress the activity of olfactory neurons.
These results suggest that proteins that confine caspases to specific regions of a cell, like the membrane, can activate the enzyme without triggering cell death. This localized, non-lethal activation lets neurons temporarily adjust their function, allowing the nervous system to adapt without needing to destroy and replace cells. The findings also highlight how important location is in guiding the activity of caspases, and it is possible that this concept may apply to other enzymes.
