Jipa, A. | Search bioRxiv

bioRxiv2025

Ubiquitination of secretory granules promotes crinophagic degradation in Drosophila

Gland cells dynamically regulate their secretory granule content via balancing the rates of synthesis, maturation, secretion, and lysosomal degradation (crinophagy). The signal(s) leading to crinophagic breakdown of secretory granules are unknown. Here we show that dynamic ubiquitination of unreleased or low-grade glue-containing secretory granules marks these vesicles for crinophagy in larval salivary gland cells of Drosophila. We identify the ubiquitin ligase Cnot4 and the deubiquitinating enzyme Usp7 as mediators of glue granule ubiquitination and deubiquitination, respectively. Loss of either Cnot4 or Usp7 impairs glue granule fusion with lysosomes. Overexpression of Cnot4 induces premature crinophagy while Usp7 overexpression prevents developmental crinophagy via modulation of glue granule ubiquitination status. Our work establishes that ubiquitination of secretory granules is a key trigger of crinophagy in Drosophila, paving the way for further analysis of this barely characterized degradation route in Metazoans.

cell biology↗

bioRxiv2024

Selective autophagy fine-tunes Stat92E activity by degrading Su(var)2-10/PIAS during glial injury signalling in Drosophila

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 following central nervous system injury to shape glial reactivity towards degenerating axons. However, the upstream regulatory mechanisms governing Stat92E activation remain elusive. Here we reveal that selective autophagy mediates 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 co-localization 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 upregulation of an innate immune pathway in glial cells following 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 for autophagy in glial immunity as part of neural injury responses.

neuroscience↗