The eye of the fly
Oeiras, 01.10.2013
ITQB researchers from the Laboratory of Cell Signaling in Drosophila and the Laboratory of Mass Spectrometry, in collaboration with researchers from Cambridge and New York Universities, have identified an essential gene for the formation of the light detecting structures in the eye of the fruit-fly. The results are now published online in Cell Reports, the novel open access journal from Cell Press.
The compound eye of Drosophila melanogaster (common fruit fly) is composed of around 800 sub-units, called ommatidia, each containing eight photoreceptor cells. Light is detected in the photoreceptor cell by the rhabdomere, a specialized organelle composed of tightly folded membrane containing rhodopsin and other proteins involved in the transduction of the light stimuli. Researchers demonstrated that in the absence of a specific gene, called Ire1, rhodopsin is not transported, rhabdomeres are not formed correctly and photoreceptor cells degenerate. In wild type flyes, Ire1 was found to be activated in the photoreceptor cells, during a critical phase of Drosophila pupal development, when the rhabdomere is formed.
Ire1 (Inositol-requiring enzyme 1) is the main mediator of the Unfolded Protein Response, a homeostatic cell response to the accumulation of unfolded (or misfolded) proteins in the endoplasmic reticulum (ER). In practice, the role of Ire1 is to ensure that protein folding inside the reticulum goes smoothly. “Each rhabdomere contains around 90% of all the membrane of the photoreceptor and a lot of protein”, explains Dina Coelho, first author in this study, “so presumably, when the rhabdomere is formed, the endoplasmic reticulum faces a huge challenge and Ire1 is activated to increase the capacity of the reticulum to deal with all the incoming proteins, such as rhodopsin and many others”.
Ire1 itself is an ER-resident transmembrane protein. The accumulation of misfolded proteins in the ER lumen activates the endoribonuclease activity present in the cytoplasmic domain of Ire1. The most well known target for Ire1 endoribonuclease activity is the mRNA encoding the Xbp1 transcription factor. Ire1 splices Xbp1 mRNA, removing a small intron and causing a frameshift in Xbp1 open reading frame. Only the Xbp1 spliced form is an effective transcription factor, activating the transcription of many target genes, including ER chaperones and folding enzymes. However, the current study shows that in the Drosophila photoreceptors, Xbp1 does not have a major role in mediating Ire1 signaling. Instead, it is another target of Ire1 endoribonuclease activity, the fatty acid transport protein (Fatp) that plays an important role as mediator of Ire1 signaling. Pedro Domingos, senior author in the paper, believes this study may also have implications for mammalian photoreceptors. Pedro also stresses that the paper was only possible due to the “great set of multidisciplinary skills available at ITQB”.
Original Article
Cell Reports, 31 October 2013 10.1016/j.celrep.2013.09.046
Xbp1-Independent Ire1 Signaling Is Required for Photoreceptor Differentiation and Rhabdomere Morphogenesis in Drosophila
Dina S. Coelho, Fatima Cairrão, Xiaomei Zeng, Elisabete Pires, Ana V. Coelho, David Ron, Hyung Don Ryoo, Pedro M. Domingos
