April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Differences in RDS Trafficking to Rod Versus Cone Outer Segments
Author Affiliations & Notes
  • S. M. Conley
    Dept. of Cell Biology, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • D. Chakraborty
    Dept. of Cell Biology, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • M. I. Naash
    Dept. of Cell Biology, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  S.M. Conley, None; D. Chakraborty, None; M.I. Naash, None.
  • Footnotes
    Support  NEI EY10609 and EY018656 (MIN), EY185122 (SMC) and the Foundation Fighting Blindness, Inc.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1102. doi:
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      S. M. Conley, D. Chakraborty, M. I. Naash; Differences in RDS Trafficking to Rod Versus Cone Outer Segments. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1102.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Mutations in the gene encoding the retinal degeneration slow (RDS) protein cause both rod- and cone-dominant retinal degenerations. We have previously shown that RDS is differentially required by the two photoreceptor subtypes and that mutation in C150 (C150S) causes protein mis-trafficking in cones but not in rods. C150 is required for RDS oligomerization and is not part of the outer segment (OS) localization sequence. The purpose of this study is to use the RDS-C150S transgenic model to elucidate differences in the rod vs. cone RDS trafficking pathway.

Methods: : Transgenic mice containing the full-length RDS cDNA with the C150S mutation and the P341Q modification (to enable recognition with mAB 3B6) driven by the cone opsin (COP) or the rod opsin promoter (MOP) were generated. Eyes were harvested at P30 and frozen retinal sections were collected. Immunohistochemistry and spinning disk confocal microscopy were used to analyze localization of proteins involved in inner segment (IS)/OS cytoskeleton and trafficking.

Results: : COP-C150S mice express C150S RDS protein only in cones and exhibit severe, dominant cone degeneration. In C150S cones, transgenic protein was mislocalized as previously described. In addition, S- and M-cone-opsins were mislocalized throughout the photoreceptor cell, but other OS membrane proteins such as the cone cyclic nucleotide gated channel were normally localized. Cytoskeletal and motor proteins such as alpha-tubulin and KIF17 were also normally localized. In contrast, the SNARE protein syntaxin 3, usually located in the IS and thought to be involved in vesicle fusion at the base of the OS, was detected abnormally localized throughout the OSs of COP-C150S cones. No alterations in protein localization were detected in the MOP-C150S model in which C150S RDS was expressed in rods.

Conclusions: : These data suggest that RDS is trafficked differently in cones than in rods. Furthermore, the mislocalization of cone opsins suggests that opsins (which do not traffick with RDS in rods) may also traffic differently in cones. Since the C150S mutation does not directly affect the OS localization sequence found in the C-terminal of RDS, but does affect the ability of RDS to oligomerize, it is possible that oligomerization in cones occurs in the inner segment (in contrast to rods) and that properly formed oligomers are required for normal trafficking. The abnormal localization of syntaxin 3 in this model suggests that the vesicle fusion step may be affected by the presence of the C150S RDS or by the absence of properly formed RDS oligomers.

Keywords: photoreceptors • retina: neurochemistry • retinal degenerations: cell biology 

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