The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in a Drosophila model of Parkinson's disease

Abstract

Parkinsons disease (PD) is a progressive neurodegenerative disorder characterized by the motor deficits, selective loss of dopaminergic (DA) neurons, and the brain accumulation of -synuclein (-syn)-composed protein aggregates called Lewy bodies (LBs). Whereas dysfunction in the protein degradation pathway, like autophagy in neurons, has been demonstrated as a critical mechanism for eliminating protein aggregates in PD, how protein aggregates are eliminated in the other brain cell type, glia, is less well characterized. In the present study, we show that Atg9, the only transmembrane protein in the core autophagy pathway, is highly expressed in Drosophila adult brain glia. Results from immunostaining and live-cell imaging analysis reveal that a significant portion of Atg9 localizes to the trans-Golgi network (TGN), autophagosomes, and lysosomes in glia; Atg9 is persistently in contact with these organelles. Lacking glial atg9 reduces the number of omegasome and autophagosome and impairs autophagic substrate degradation, suggesting that glial Atg9 participates in the early steps of autophagy, hence the control of autophagic degradation. Importantly, loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive DA neuron loss and locomotion deficits. Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and PD. These results provide new insights on the underlying mechanism of PD.