RNA-seq raw data and analysis for APP, Shal495 and TrpA1 Drosophila melanogaster mutants

Evidence suggests that impaired synaptic and firing homeostasis represents a driving force of early Alzheimer's disease (AD) progression. Here, we examine synaptic and sleep homeostasis in a Drosophila model by overexpressing human amyloid precursor protein (APP), whose duplication and mutations cause familial early-onset AD. We find that APP overexpression induces synaptic hyperexcitability. RNA-seq data indicate exaggerated expression of Ca2+ related signaling genes in APP mutants, including genes encoding Dmca1D, calcineurin (CaN) complex, and IP3R, but not in hyperexcitable mutants caused by TrpA1 or Shal/Kv4. We further demonstrate that increased CaN activity triggers transcriptional activation of Itpr (IP3R) through activating nuclear factor of activated T cells (NFAT). Strikingly, APP overexpression causes defects in both synaptic downscaling and sleep deprivation induced sleep rebound, and both defects could be restored by inhibiting IP3R. Our findings uncover IP3R as a shared signaling molecular in synaptic downscaling and sleep homeostasis, and its dysregulation may lead to synaptic hyperexcitability and AD progression at early stage. Overall design: We performed RNA sequencing (RNA-seq) on dissociated adult heads (5-7 days) to explore the possible downstream pathways that might be affected by APP, Shal495, TrpA1 and hyperexcitability induced in these mutants. For each sample, total RNA was isolated from approximately 50 adult male heads.