title: Structure and function in rhodopsin. 7. Point mutations associated with autosomal dominant retinitis pigmentosa.
abstract: Autosomal dominant retinitis pigmentosa (ADRP) is a hereditary form of retinitis pigmentosa which accounts for about 15% of all types of the latter disease. Recently, close to 50 mutations, mostly point mutations, have been identified in the rhodopsin gene in ADRP patients. We have introduced these mutations in the synthetic bovine rhodopsin gene and herein report on the expression of the mutant genes in COS-1 cells and studies in vitro of the properties of the expressed opsins. The mutant phenotypes fall into three classes: Class I mutants are expressed in COS-1 cells at wild-type levels, form the normal rhodopsin chromophore with 11-cis-retinal, and are transported to the cell surface. However, on illumination, they activate transducin inefficiently. Class II mutants remain in the endoplasmic reticulum and do not bind 11-cis-retinal to form the chromophore. Class III mutants are expressed at low levels and form rhodopsin chromophore only poorly. They also remain in the endoplasmic reticulum and, as expected, show high mannose glycosylation. Nearly all of the mutants studied show abnormal sensitivity to light compared to the wild type, and they activate transducin less efficiently. We conclude that the majority of the ADRP mutants have folding defects.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge.
authors.forename: S
authors.initials: S
authors.lastname: Kaushal
authors.forename: H G
authors.initials: HG
authors.lastname: Khorana
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018014:Gene Transfer Techniques; D006031:Glycosylation; D008358:Mannose / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010777:Photochemistry; D017354:Point Mutation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012172:Retinaldehyde / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D012243:Rhodopsin; D008358:Mannose; D012172:Retinaldehyde