Zonda: a novel gene involved in autophagy and growth control

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

San Diego

Conferencia; . 55th Annual Drosophila Research Conference; 2014

The final size of an organism, its organs and cells is controlled by the interconnection of intrinsic genetic information with external environmental clues. We describe the function of a novel Drosophila gene, zonda, as a negative regulator of growth. The loss of zonda activity in the head generates flies with larger heads than controls. Conversely, overexpression of zonda leads to a pinhead phenotype, and mosaic overexpression of zonda in larval fat body cells provokes an autonomous cell size reduction. These effects on cell growth correlate with the phosphorylation state of S6K, the target of the TOR kinase. Zonda subcellular localization is sensitive to nutrients. In well-fed larvae Zonda presents a vesiculo-reticulated subcelullar distribution. Zonda relocalizes upon starvation to discrete foci that co-localize with autophagosome marker ATG-8. Starvation-induced Zonda nucleation depends on ATG1 but not on VPS34, unlike ATG8 nucleation that fully depends on both, suggesting that Zonda nucleation is an early event in the autophagic cascade. Starved zonda mutant cells fail to incorporate lysotracker and to nucleate ATG8, indicating a requirement of zonda activity for this process. zonda over-expression is sufficient to induce autophagy, as assessed by the nucleation of ATG8. zonda mammalian homolog is also required for starvation-induced autophagy and it also stimulates ATG8 nucleation when overexpressed. We postulate that Zonda effects on cell growth are a consequence of its capability to regulate autophagy. Altogether, zonda is a novel autophagy gene likely to play a role at early steps of the autophagic cascade, and its role on autophagy is evolutionary conserved.