Selective autophagy fine-tunes Stat92E activity by degrading Su(var)2-10/PIAS in Drosophila glia.

Glial immunity plays a pivotal role in the maintenance of nervous system homeostasis and in responses to stress conditions, including neural injuries. The transcription factor Stat92E is activated independently of the canonical JAK/STAT pathway in Drosophila glial cells after brain injury to shape glial reactivity toward degenerating axons. However, the upstream regulatory mechanisms governing Stat92E activation remain elusive. Here, we reveal that selective autophagy gates nuclear translocation of Stat92E after injury and directs the degradation of the PIAS SUMO ligase family member Stat92E repressor, Su(var)2-10, in glia. Autophagic elimination of Su(var)2-10 mediated by its colocalization and interaction with the core autophagy factor Atg8a is required for efficient Stat92E-dependent transcription after injury. In line with this, we demonstrate that autophagy is essential for the up-regulation of an innate immune pathway in glial cells after axon injury, characterized by the induction of virus-induced RNA 1 (vir-1). We propose that autophagic Su(var)2-10 breakdown controls Stat92E activation to allow glial reactivity. These findings identify a critical role of autophagy in glial immunity as part of nervous system injury responses.