Zonda: A Novel Drosophila Gene Involved in Autophagy and Vesicle Trafficking.

MARIANA MELANI; NURIA M. ROMERO; JULIETA MARIA ACEVEDO; PABLO WAPPNER

Puerto Natales

Taller; Current advances in membrane trafficking: Implications for polarity and diseases; 2014

EMBO

We describe the function of zonda (Zda), a novel Drosophila gene involved in autophagy. Zda encodes a putative chaperone from the immunophilin superfamily with a putative transmembrane domain. Zda subcellular localization is sensitive to nutrients: Whereas in well-fed larvae it presents a vesiculo-reticulated cytoplasmic distribution, upon starvation, Zda concentrates in discrete foci that fully co-localize with ATG-8 and partially co-localize with lysotracker and Lamp1. Starvation-induced nucleation of Zda depends on ATG1 but not on VPS34, suggesting that it is involved in an early event of the autophagic cascade. In starved 3rd instar larvae, Zda mutant cells fail to incorporate lysotracker and to nucleate ATG8, indicating that Zda is absolutely required for autophagy. Over-expression of Zda is sufficient to promote nucleation of ATG8, suggesting that Zda functions at a hierarchical level comparable to that of ATG1. It has been shown in Drosophila that autophagy restrains cell growth in well-fed individuals, and consistent with this, we found that Zda is a negative regulator of growth: the loss of Zda in the head leads to head overgrowth, and conversely, overexpression of Zda in various tissues provokes autonomous cell size reduction. In summary, our results indicate that Zda is a novel autophagy gene that likely plays a role in early steps of the autophagic cascade that regulates growth in a cell autonomous manner.