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Nansi Colley, Erica Rosenbaum, Kimberely Brehm, Eva Vasiljevic; The Drosophila SNARE Protein, Gos28, is Critical for Rhodopsin Transport and Photoreceptor Viability. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2645.
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The purpose of this study was to determine the role of the Golgi SNARE protein, Gos28, in the vesicular transport of rhodopsin during its biosynthesis and to examine the mechanisms by which mutations in gos28 lead to retinal degeneration in the common fruit fly, Drosophila.
We used Drosophila as a model organism to study the mechanisms of vesicular transport of rhodopsin and how defects in this process cause retinal degeneration.
Here, we show that in Drosophila, the Golgi SNARE protein, Gos28, plays a critical role in the vesicular transport of rhodopsin during its biosynthesis. We demonstrate that null mutations in gos28 lead to the accumulation of rhodopsin in the secretory pathway and cause a late-onset retinal degeneration. In the gos28 mutant rhodopsin is detected in an immature, hyper-glycosylated form, which is indicative of defects in rhodopsin trafficking. Furthermore, this hyper-glycosylated immature form of rhodopsin is insensitive to treatment with endoglycosidase H (Endo H), providing evidence that rhodopsin has successfully reached the cis-Golgi. However, because rhodopsin fails to undergo trimming events that occur in the Golgi, our data suggest that rhodopsin does not effectively exit the trans-Golgi. These results indicate that Gos28 is required for transport events between the sub-compartments of the Golgi. In order to study the structure/function of Gos28 in vivo, we used site-directed mutagenesis and generated a collection of transgenic flies expressing Gos28 mutations. More specifically, we analyzed animals that express Gos28 lacking its transmembrane domain or harboring one of several different point mutations in the SNARE domain. Our mutant analyses have provided information on residues that are important for Gos28 function as a SNARE protein during vesicle fusion and rhodopsin biosynthesis.
We have shown that the SNARE protein, Gos28, plays a critical role in the vesicular transport of rhodopsin during its biosynthesis in Drosophila. Mutations in gos28 lead to defects in rhodopsin maturation causing rhodopsin to accumulate abnormally in the secretory pathway resulting in retinal degeneration. Our work points to the importance of SNARE proteins in rhodopsin maturation as well as for photoreceptor cell survival and provides insights into mechanisms of retinal degeneration.
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