UMMS Affiliation
Department of Ophthalmology; Horae Gene Therapy Center
Publication Date
2016-04-15
Document Type
Article
Disciplines
Biochemistry | Eye Diseases | Genetics and Genomics | Medical Genetics | Molecular Biology | Ophthalmology
Abstract
Mutations inRPGR(ORF15)(retinitis pigmentosa GTPase regulator) are a major cause of inherited retinal degenerative diseases. RPGR(ORF15)(1152 residues) is a ciliary protein involved in regulating the composition and function of photoreceptor cilia. The mutational hotspot in RPGR(ORF15)is an unusual C-terminal domain encoded by exon ORF15, which is rich in polyglutamates and glycine residues (Glu-Gly domain) followed by a short stretch of basic amino acid residues (RPGR(C2)domain; residues 1072-1152). However, the properties of the ORF15-encoded domain and its involvement in the pathogenesis of the disease are unclear. Here we show that RPGR(ORF15)is glutamylated at the C-terminus, as determined by binding to GT335, which recognizes glutamylated substrates. This reactivity is lost in two mouse mutants ofRpgr, which do not express RPGR(ORF15)due to disease-causing mutations in exon ORF15. Our results indicate that RPGR(ORF15)is posttranslationally glutamylated in the Glu-Gly domain and that the GT335 antibody predominantly recognizes RPGR(ORF15)in photoreceptor cilia.
Keywords
Cilia, GT335, Glutamylation, RPGR, Retina
Rights and Permissions
Copyright © 2016. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
DOI of Published Version
10.1242/bio.016816
Source
Biol Open. 2016 Apr 15;5(4):424-8. doi: 10.1242/bio.016816. Link to article on publisher's site
Journal/Book/Conference Title
Biology open
Related Resources
PubMed ID
26941104
Repository Citation
Rao, Kollu N.; Anand, Manisha; and Khanna, Hemant, "The carboxyl terminal mutational hotspot of the ciliary disease protein RPGRORF15 (retinitis pigmentosa GTPase regulator) is glutamylated in vivo" (2016). Open Access Articles. 2739.
https://escholarship.umassmed.edu/oapubs/2739
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Included in
Biochemistry Commons, Eye Diseases Commons, Genetics and Genomics Commons, Medical Genetics Commons, Molecular Biology Commons, Ophthalmology Commons