title: Glycosylation of rhodopsin is necessary for its stability and incorporation into photoreceptor outer segment discs.
abstract: Rhodopsin, a G-protein coupled receptor, most abundant protein in retinal rod photoreceptors, is glycosylated at asparagines-2 and 15 on its N-terminus. To understand the role of rhodopsin's glycosylation in vivo, we generated and characterized a transgenic mouse model that expresses a non-glycosylated form of rhodopsin. We show that lack of glycosylation triggers a dominant form of progressive retinal degeneration. Electron microscopic examination of retinas at postnatal day 17 revealed the presence of vacuolar structures that distorted rod photoreceptor outer segments and became more prominent with age. Expression of non-glycosylated rhodopsin alone showed that it is unstable and is regulated via ubiquitin-mediated proteasomal degradation at the base of outer segments. We observed similar vacuolization in outer segments of transgenic mice expressing human rhodopsin with a T17M mutation (hT17M), suggesting that the mechanism responsible for the degenerative process in mice expressing the non-glycosylated rhodopsin and the RHO(hT17M) mice is likely the cause of phenotype observed in retinitis pigmentosa patients carrying T17M mutation.
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Anne R
authors: AR
authors: Murray
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Linda
authors: L
authors: Vuong
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Daniel
authors: D
authors: Brobst
authors: Research Service, VA Western New York Healthcare System, and Departments of Ophthalmology and Biochemistry, University of Buffalo/State University of New York, Buffalo, NY 14215, USA.
authors: Steven J
authors: SJ
authors: Fliesler
authors: Ophthalmic Research, Cleveland Clinic, Research Service, Cleveland VA Medical Center, Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA and.
authors: Neal S
authors: NS
authors: Peachey
authors: Department of Vision Sciences, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors: Marina S
authors: MS
authors: Gorbatyuk
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Muna I
authors: MI
authors: Naash
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA, muayyad-al-ubaidi@ouhsc.edu.
authors: Muayyad R
authors: MR
authors: Al-Ubaidi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D020125:Mutation, Missense; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism* / Q000502:physiology; D054875:Ubiquitination
chemical_list: D012243:Rhodopsin
references: J Neurosci. 2000 Aug 1;20(15):5733-40
references: 10908613
references: J Biol Chem. 2000 Aug 11;275(32):24752-9
references: 10811808
references: Invest Ophthalmol Vis Sci. 2001 Mar;42(3):589-600
references: 11222515
references: J Biol Chem. 2002 Nov 15;277(46):44566-75
references: 12215439
references: J Hered. 2003 Jan-Feb;94(1):27-30
references: 12692159
references: Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2514-21
references: 15277471
references: Hum Mol Genet. 2004 Sep 15;13(18):2075-87
references: 15254014
references: J Cell Biol. 1985 Feb;100(2):574-87
references: 3155750
references: Invest Ophthalmol Vis Sci. 2012 Jan;53(1):361-73
references: 22076989
references: Invest Ophthalmol Vis Sci. 2012 Jun;53(7):3792-800
references: 22589437
references: PLoS One. 2012;7(6):e39702
references: 22745813
references: Clin Genet. 2013 Aug;84(2):132-41
references: 23701314
references: Invest Ophthalmol Vis Sci. 1985 Oct;26(10):1386-404
references: 2931395
references: J Histochem Cytochem. 1986 Jan;34(1):5-16
references: 2934469
references: Exp Eye Res. 1986 Jan;42(1):55-71
references: 2420630
references: J Biol Chem. 1990 Nov 25;265(33):20563-9
references: 1978723
references: Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8484-8
references: 8378322
references: J Biol Chem. 1993 Dec 15;268(35):26645-9
references: 8253795
references: J Biol Chem. 1996 Jun 14;271(24):14473-84
references: 8662797
references: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11933-8
references: 9751768
references: Nat Genet. 1998 Dec;20(4):344-51
references: 9843205
references: Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):736-41
references: 9892703
references: J Biol Chem. 2004 Dec 17;279(51):53828-39
references: 15459196
references: J Biol Chem. 2005 Jan 14;280(2):1284-91
references: 15509574
references: Arch Ophthalmol. 2007 Feb;125(2):151-8
references: 17296890
references: J Neurosci. 2009 Feb 18;29(7):2297-308
references: 19228982
references: J Neurosci. 2009 Dec 2;29(48):15145-54
references: 19955366
references: Eur J Neurosci. 2010 Nov;32(9):1461-72
references: 21039965