title: Xbp1-independent Ire1 signaling is required for photoreceptor differentiation and rhabdomere morphogenesis in Drosophila.
abstract: The unfolded protein response (UPR) is composed by homeostatic signaling pathways that are activated by excessive protein misfolding in the endoplasmic reticulum. Ire1 signaling is an important mediator of the UPR, leading to the activation of the transcription factor Xbp1. Here, we show that Drosophila Ire1 mutant photoreceptors have defects in the delivery of rhodopsin-1 to the rhabdomere and in the secretion of Spacemaker/Eyes Shut into the interrhabdomeral space. However, these defects are not observed in Xbp1 mutant photoreceptors. Ire1 mutant retinas have higher mRNA levels for targets of regulated Ire1-dependent decay (RIDD), including for the fatty acid transport protein (fatp). Importantly, the downregulation of fatp by RNAi rescues the rhodopsin-1 delivery defects observed in Ire1 mutant photoreceptors. Our results show that the role of Ire1 during photoreceptor differentiation is independent of Xbp1 function and demonstrate the physiological relevance of the RIDD mechanism in this specific paradigm.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República, 2780-157 Oeiras, Portugal.
authors.forename: Dina S
authors.initials: DS
authors.lastname: Coelho
authors.forename: Fatima
authors.initials: F
authors.lastname: Cairrão
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zeng
authors.forename: Elisabete
authors.initials: E
authors.lastname: Pires
authors.forename: Ana V
authors.initials: AV
authors.lastname: Coelho
authors.forename: David
authors.initials: D
authors.lastname: Ron
authors.forename: Hyung Don
authors.initials: HD
authors.lastname: Ryoo
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Domingos
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D010786:Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C517798:Xbp1 protein, Drosophila; D004722:Endoribonucleases; C511918:inositol requiring enzyme-1, Drosophila