title: Varying the GARP2-to-RDS Ratio Leads to Defects in Rim Formation and Rod and Cone Function.
abstract: OBJECTIVE
  The beta subunit of the rod cyclic nucleotide gated channel B1 (CNGB1) contains a proline/glutamic acid-rich N-terminal domain (GARP), which is also present in rods as a non-membrane-bound protein (GARP1/2). GARP2 and CNGB1 bind to retinal degeneration slow (RDS), which is present in the rims of rod and cone outer segment (OS) layers. Here we focus on the importance of RDS/GARP complexes in OS morphogenesis and stability.
  
  
  METHODS
  Retinal structure, function, and biochemistry were assessed in GARP2-Tg transgenic mice crossed onto rds+/+, rds+/-, and rds-/- genetic backgrounds.
  
  
  RESULTS
  GARP2 expression decreased in animals with reduced RDS levels. Overexpression of GARP2 led to abnormalities in disc stacking in GARP2-Tg/rds+/+ and the accumulation of abnormal vesicular structures in GARP2-Tg/rds+/- OS, as well as alterations in RDS-ROM-1 complex formation. These abnormalities were associated with diminished scotopic a- and b-wave amplitudes in GARP2-Tg mice on both the rds+/+ and rds+/- backgrounds. In addition, severe defects in cone function were observed in GARP2-Tg mice on all RDS backgrounds.
  
  
  CONCLUSIONS
  Our results indicate that overexpression of GARP2 significantly exacerbates the defects in rod function associated with RDS haploinsufficiency and leads to further abnormalities in OS ultrastructure. These data also suggest that GARP2 expression in cones can be detrimental to cones. RDS/GARP interactions remain under investigation but are critical for both OS structure and function.
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, University of Alabama at Birmingham, Birmingham, Alabama, United States.
authors.forename: Marci L
authors.initials: ML
authors.lastname: DeRamus
authors.affiliation: Department of Vision Sciences, 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; D015153:Blotting, Western; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D004596:Electroretinography; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology* / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578919:glutamic acid-rich protein-2, human; D004247:DNA