Drosophila pecanex activates Notch signaling via unfolded protein response (UPR). Tomoko Yamakawa¹, Yu Atsumi¹, Takeshi Sasamura¹, Naotaka Nakazawa¹, Emiko Suzuki², Mark E. Fortini³, Kenji Matsuno¹. 1) Osaka Univ, Osaka, Japan; 2) Gene Network Lab, NIG, Japan; 3) Thomas Jefferson Univ, Philadelphia, USA.

   Notch (N) signaling is an evolutionarily conserved mechanism that regulates a broad spectrum of cell-specification through local cell-cell interaction. The homozygous mutant flies of pecanex (pcx) are viable, but pcx homozygous females mated with the pcx mutant males produce embryos that show an N-like neurogenic phenotype, suggesting that pcx encodes a component of N signaling. Pcx is a multi-pass membrane protein. However, its biochemical functions are still unknown.
  Here we established that Pcx is a component of the N-signaling pathway. Pcx was required upstream of activated form of N, probably in N-signal-receiving cells, suggesting that pcx is required prior to or during the activation of N. We found that Pcx was an endoplasmic reticulum (ER) residential protein. In addition, ER was enlarged in the embryos homozygous for pcx lacking its maternal contribution. However, such ER enlargement was not observed in embryos homozygous for N or Presenilin. These results suggest that the ER enlargement is not due to the disruption of N signaling.
  Hyper-induction of the unfolded protein response (UPR), by the expression of activated Xbp1 or dominant-negative Heat-shock cognate 70-3, suppressed the neurogenic phenotype and ER enlargement caused by the absence of pcx. A similar suppression of these phenotypes was increased by the overexpression of O-fucosyltransferase 1, an N-specific chaperon. Taking these results together, we speculate that the reduction of N signaling in embryos lacking pcx function might be attributable to defective ER functions, which are compensated for by up-regulation of the UPR and possibly by enhancing N folding.