An autophagy-based release pathway regulates synaptic plasticity

What is it about?

Neurons can rapidly remodel their synaptic morphology and function to adapt to changes in various stimuli, a process known as activity-induced synaptic remodeling. Understanding this dynamic process provides insights into learning, memory formation, and pathological changes in brain diseases. To identify new molecular pathways important for this process, we conducted a genetic screen in Drosophila, utilizing a collection of stocks containing RNAi against disease-causing genes conserved between flies and humans. We uncovered a process called secretory autophagy that allows neurons to rapidly coordinate activity-induced synaptic remodeling.

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Photo by Hal Gatewood on Unsplash

Photo by Hal Gatewood on Unsplash

Why is it important?

Secretory autophagy is a poorly understood cellular process that releases contents found within autophagosomes extracellularly, rather than undergoing conventional degradative pathway. While it was previously thought to be triggered in response to infection or stress, we have demonstrated that secretory autophagy release can also be activated by neuronal activity to regulate synaptic remodeling. Furthermore, we found that secretory autophagy mutants exhibit malfunctions in synaptic potentiation. Overall, this finding unveils a new mechanism regulating synaptic plasticity and paves the way for a better understanding of how neurons communicate to coordinate activity-dependent changes.

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