The Function of Oligomerization-Incompetent RDS in Rods

  • Dibyendu Chakraborty
  • Shannon M. Conley
  • Steven J. Fliesler
  • Muna I. Naash
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 664)


The photoreceptor-specific tetraspanin glycoprotein RDS (retinal degeneration slow) is associated with many forms of inherited retinal disease. RDS shares features in common with other tetraspanin proteins, including the existence of a large intradiscal D2 loop containing several cysteines. While these cysteines are used only for intramolecular disulfide bonds in most tetraspanins, RDS expresses a seventh, unpaired cysteine (C150) used for intermolecular disulfide bonding in the formation of large RDS oligomers. To study oligomerization-dependent vs. oligomerization-independent RDS functions in rods, we generated a transgenic mouse line harboring a point mutation that replaces this Cys with Ser (C150S), leading to the expression of an RDS protein that cannot form intermolecular disulfide bonds. The mouse opsin promoter (MOP) was used to direct C150S RDS expression specifically in rods in these transgenic mice (MOP-T). Here we report improvement in scotopic ERGs in MOP-T/rds +/– mice (compared to non-transgenic rds +/– controls) and the appearance of malformed outer segments (OSs) in MOP-T mice that do not express native RDS (MOP-T/rds –/– ). These results suggest that while normal OS structure and function require RDS oligomerization, some RDS function is retained in the absence of C150. Since one of the functions of other tetraspanin proteins is to promote assembly of a membrane microdomain known as the “tetraspanin web”, future studies may investigate whether assembly of this web is one of RDS’s oligomerization-independent functions.


Outer Segment Retinal Degeneration Retinal Function Intermolecular Disulfide Bond Outer Segment Disc 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The monoclonal antibodies for this study (1D4) were generously shared with us by Dr. Robert Molday, University of British Columbia. The authors would like to thank Rasha Makkia for her excellent technical assistance with the transgenic animals. This study was supported by grants from the National Institutes of Health (EY10609 & EY018656 to MIN; EY007361 to SJF; Core Grant for Vision Research EY12190 to MIN), the Foundation Fighting Blindness (MIN), the Knights Templar Eye Research Foundation (DC) and a departmental Unrestricted Grant from Research to Prevent Blindness (SJF). Dr. Naash is the recipient of a Research to Prevent Blindness James S. Adams Scholar Award. Dr. Fliesler is the recipient of a Research to Prevent Blindness Senior Scientist Award.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Dibyendu Chakraborty
    • 1
  • Shannon M. Conley
    • 1
  • Steven J. Fliesler
    • 2
  • Muna I. Naash
    • 1
  1. 1.Department of Cell BiologyUniversity of Oklahoma Health Sciences CenterOklahomaUSA
  2. 2.Veterans Administration Western New York Healthcare System, and the Department of Ophthalmology and BiochemistryUniversity at Buffalo (State University of New York)BuffaloUSA

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