ZONDA: A NOVEL GENE INVOLVED IN AUTOPHAGY AND GROWTH CONTROL IN Drosophila

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

Chascomús

Jornada; XV Jornadas Anuales de la Sociedad Argentina de Biología; 2013

Understanding the mechanisms by which multicellular organisms control the growth of cells, organs and the whole body is a central question in developmental biology. Genetic mechanisms interlace with environmental clues to establish the final size of the organism. We describe the function of a novel Drosophila gene, zonda, as a negative regulator of growth. eyeless-flippase-induced zonda mutant clones generate larger heads when compared to controls. Conversely, overexpression of zonda in the head tissue leads to a pinhead phenotype, and mosaic overexpression of zonda in larval fat body cells provokes an autonomous reduction in cell size. Strikingly, Zonda subcellular localization is sensitive to the nutritional status of the larvae. In well-fed individuals Zonda presents a vesiculo-reticulated subcelullar distribution. When third instar larvae are fasted for 4 hours, Zonda distribution changes dramatically to discrete foci. Zonda-containing foci partially co-localize with lysotracker and Lamp1 positive vesicles, and strongly co-localize with ATG-8, indicating that under these conditions Zonda is part of autophagy-induced structures. This remarkable co-localization led us to investagate a potential role for Zonda as an autophagy gene. Indeed, we found that Zonda mutant clones in the fat body of starved third instar larvae fail to incorporate lysotracker, characteristic of starvation-induced autophagy. Even more, over-expression of Zonda is sufficient to induce autophagy, as assessed by the nucleation of ATG8 in autophagosomes. Our results reveal that Zonda is a novel autophagy gene likely to play a role at early steps of the autophagy cascade, with the capability to impact cell size.