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B.L. Krock, B.D. Perkins; The Intraflagellar Transport Protein IFT57 Is Required for Outer Segment Maintenance in Vertebrate Photoreceptors . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4184.
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© ARVO (1962-2015); The Authors (2016-present)
Protein transport to the developing and mature photoreceptor outer segment is mediated by the multi–subunit Intraflagellar Transport (IFT) particle. It is currently unclear if all subunits of the IFT complex are required for photoreceptor outer segment formation and the specific role individual IFT proteins may play in this process. The purpose of this study was to analyze zebrafish with mutations in the IFT57 and IFT88 subunits of the IFT particle for defects in photoreceptor morphogenesis and protein transport. The observed phenotypic differences observed between these IFT mutants suggest that individual IFT proteins have distinct functions in photoreceptor outer segment formation.
Light and transmission electron microscopy was used to assess photoreceptor outer segment formation and structure in wild type and IFT57 and IFT88 zebrafish mutants at 4–5 days post fertilization. The localization of rhodopsin and cone opsins was examined by immunohistochemistry to assess protein transport to the outer segment. Photoreceptor structure was further analyzed immunohistochemically using phalloidin and acetylated tubulin staining to visualize ciliary structures.
IFT88 mutants fully lack all photoreceptor outer segments. IFT57 mutants form photoreceptor outer segments that are 70% shorter than wild type, indicating that IFT57 is required for outer segment maintenance whereas IFT88 is required for outer segment formation. Disk membrane organization is normal in the photoreceptor outer segments of IFT57 mutants, indicating that IFT57 is not required for the initial assembly of outer segments, but for long–term maintenance and growth. IFT57 mutants exhibit defects in rhodopsin transport, while IFT88 mutants display complete rhodopsin mislocalization. IFT57 mutants form green, blue and UV cone photoreceptors, but their respective opsins are also mislocalized. Finally, IFT57 mutants form ciliary structures that extend from the apical surface of the cell, while these structures were not observed in IFT88 mutants.
It is widely assumed that the IFT proteins function in an all–or–none fashion during cilia formation in all cells, including photoreceptors. Our results demonstrate that IFT57 regulates photoreceptor outer segment outgrowth and maintenance, but not the initial cilia assembly. This is likely achieved through a specific function of IFT57 within the IFT complex. Our study suggests that mutations in different IFT proteins can affect different aspects of photoreceptor development, which has implications in the pathology of photoreceptor degenerative disorders.
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