Human Molecular Genetics Advance Access originally published online on December 2, 2008
Human Molecular Genetics 2009 18(5):797-808; doi:10.1093/hmg/ddn406
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Differential requirements for retinal degeneration slow intermolecular disulfide-linked oligomerization in rods versus cones
1 Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA 2 Departments of Ophthalmology and Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104, USA
* To whom correspondence should be addressed at: Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB 781, Oklahoma City, OK 73126-0901, USA. Tel: +1 4052718001 ext 47969; Fax: +1 4052713548; Email: muna-naash{at}ouhsc.edu.
Received October 6, 2008; Revised November 13, 2008; Accepted November 27, 2008
It is commonly assumed that the ultrastructural organization of the rim region of outer segment (OS) discs in rods and lamellae in cones requires functional retinal degeneration slow/rod outer segment membrane protein 1 (Rds/Rom-1) complexes. Cysteine-150 (C150) in Rds has been implicated in intermolecular disulfide bonding essential for functional Rds complexes. Transgenic mice containing the Rds C150S mutation (C150S-Rds) failed to form higher-order Rds oligomers, although interactions between C150S-Rds and Rom-1 occurred in rods, but not in cones. C150S-Rds mice exhibited marked early-onset reductions in cone function and abnormal OS structure. In contrast, C150S-Rds expression in rods partly rescued the rds+/– phenotype. Although C150S-Rds was detected in the OSs in rods and cones, a substantial percentage of C150S-Rds and cone opsins were mislocalized to different cellular compartments in cones. The results of this study provide novel insights into the importance of C150 in Rds oligomerization and the differences in Rds requirements in rods versus cones. The apparent OS structural differences between rods and cones may cause cones to be more susceptible to the elimination of higher-order Rds/Rom-1 oligomers (e.g. as mediated by mutation of the Rds C150 residue).
Present address: Department of Ophthalmology (Ross Eye Institute), University at Buffalo, SUNY, Buffalo, NY, USA and Research Service, Veterans Administration, Western New York Healthcare System, Buffalo, NY 14215, USA.