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 KN, Anand M, Khanna H. (2016). The carboxyl terminal mutational hotspot of the ciliary disease protein RPGRORF15 (retinitis pigmentosa GTPase regulator) is glutamylated in vivo. Open Access Articles. https://doi.org/10.1242/bio.016816. Retrieved from 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