title: Role of RDS and Rhodopsin in Cngb1-Related Retinal Degeneration.
abstract: OBJECTIVE
  Rod photoreceptor outer segment (OS) morphogenesis, structural integrity, and proper signal transduction rely on critical proteins found in the different OS membrane domains (e.g., plasma, disc, and disc rim membrane). Among these key elements are retinal degeneration slow (RDS, also known as peripherin-2), rhodopsin, and the beta subunit of the cyclic nucleotide gated channel (CNGB1a), which have been found to interact in a complex. The purpose of this study was to evaluate the potential interplay between these three proteins by examining retinal disease phenotypes in animal models expressing varying amounts of CNGB1a, rhodopsin, and RDS.
  
  
  METHODS
  Outer segment trafficking, retinal function, and photoreceptor structure were evaluated using knockout mouse lines.
  
  
  RESULTS
  Eliminating Cngb1 and reducing RDS leads to additive defects in RDS expression levels and rod electroretinogram (ERG) function, (e.g., Cngb1-/-/rds+/- versus rds+/- or Cngb1-/-) but not to additive defects in rod ultrastructure. These additive effects also manifested in cone function: Photopic ERG responses were significantly lower in the Cngb1-/-/rds+/- versus rds+/- or Cngb1-/-, suggesting that eliminating Cngb1 can accelerate the cone degeneration that usually presents later in the rds+/-. This was not the case with rhodopsin; reducing rhodopsin levels in concert with eliminating CNGB1a did not lead to phenotypes more severe than those observed in the Cngb1 knockout alone.
  
  
  CONCLUSIONS
  These data support a role for RDS as the core component of a multiprotein plasma membrane-rim-disc complex that has both a structural role in photoreceptor OS formation and maintenance and a functional role in orienting proteins for optimal signal transduction.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Dibyendu
authors.initials: D
authors.lastname: Chakraborty
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Conley
authors.affiliation: Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama, United States.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Pittler
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, Texas, United States.
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000096:biosynthesis / Q000235:genetics*; D004596:Electroretinography; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D064531:Peripherins / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012243:Rhodopsin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C529481:Cngb1 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D009419:Nerve Tissue Proteins; D064531:Peripherins; C578996:Prph2 protein, mouse; D012313:RNA; D012243:Rhodopsin