Drosophila ataxin-2 gene encodes two differentially expressed isoforms and its function in larval fat body is crucial...

Different isoforms of ataxin-2 are predicted in Drosophila and may underlie different cellular processes. Here, we validated the isoforms B and C of Drosophila ataxin-2 locus (dAtx2), which we found to be expressed in various tissues and at different levels during development. dAtx2-B mRNA was detected at low amounts during all developmental stages, whereas dAtx2-C mRNA levels increase by eightfold from L3 to pupal-adult stages. Higher amounts of dAtx2-B protein were detected in embryos, while dAtx2-C protein was also expressed in higher levels in pupal-adult stages, indicating post-transcriptional control for isoform B and transcription induction for isoform C, respectively. Moreover, in the fat body of L3 larvae dAtx2-C, but not dAtx2-B, accumulates in cytoplasmic foci that colocalize with sec23, a marker of endoplasmic reticulum exit sites (ERES). Interestingly, animals subjected to selective knockdown of dAtx2 in the larval fat body do not complete metamorphosis and die at the third larval stage or early puparium. Additionally, larvae knocked down for dAtx2, grown at 29 °C, are significantly smaller than control animals due to reduction in DNA replication and cell growth, which are consistent with the decreased levels of phosphorylated-AKT observed in the fat body. Based on the localization of ataxin-2 (dAtx2-C) in ERESs, and on the phenotypes observed by dAtx2 knockdown in the larval fat body, we speculate a possible role for this protein in processes that regulate ERES formation. These data provide new insights into the biological function of ataxin-2 with potential relevance to neurodegenerative diseases.