Importance of unfolded proteins in blindness
A maze of membranes in the cell, the endoplasmic reticulum (ER) is the site of synthesis of membrane proteins. When protein folding is impaired, the unfolded or misfolded molecules cause stress on the cell, ER stress. Response to this, the unfolded protein response (UPR), is the root cause of RP where the photoreceptor cells degenerate over time. The 'ER stress and photoreceptor degeneration in Drosophila' (DROSOERSTRESS) project has investigated the role of UPR in the faulty production of the light-sensitive pigment rhodopsin. The research team looked at mutations in ninaE in Drosophila, the fruit fly gene that codes for rhodopsin production. As a signalling pathway, IRE1/Xbp1 has been shown to offer protection against ninaE-induced photoreceptor degeneration. The DROSOERSTRESS scientists looked at this biochemical cascade in particular. Results showed that Ire1 mutants have defects in delivery of rhodopsin to the rhabdomere, a key area in the retina. However, this problem is not apparent in Xbp1 mutants. Down regulation of a fatty acid transport protein — part of the regulated Ire1-dependent decay repair mechanism — rescues the faulty delivery of the pigment in Ire1 mutants. Overall, the research showed that Ire1 and Xbp1 are independent of each other in photoreceptor development. DROSOERSTRESS results promise to have great relevance for human health. ER stress is a very important factor in RP and many other neurodegenerative disorders.
Keywords
Retinitis pigmentosa, protein folding, ER stress, photoreceptor degeneration, rhodopsin
