Peter Soba (University of Erlangen)

Axon length-dependent synapse loss by cytokine-induced glial phagocytosis

Host: Sebastian Rumpf

Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors. Nevertheless, the cellular and molecular bases for neurite length-dependent vulnerability of neurons to degeneration is largely unknown. We took advantage of Drosophila an in vivo model and show that activation of the integrated stress response (ISR) triggers an intrinsic conserved program resulting in axon length-dependent synapse loss. ISR activation in neurons recruits phagocytic glia via cytokine-induced STAT signaling, resulting in preferential synapse removal on neurons with long axons. Finally, we found that axon length-dependent presynapse loss in fly models of human NDDs utilized this pathway. Our data suggest an intrinsic neuronal tag priming neurons with long axons for synapse removal under conditions linked to neuronal stress and NDDs.

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