UMMS Affiliation

Department of Ophthalmology; Horae Gene Therapy Center

Publication Date

4-15-2016

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.

Rights and Permissions

Citation: Biol Open. 2016 Apr 15;5(4):424-8. doi: 10.1242/bio.016816. Link to article on publisher's site

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

Related Resources

Link to Article in PubMed

Keywords

Cilia, GT335, Glutamylation, RPGR, Retina

Journal/Book/Conference Title

Biology open

PubMed ID

26941104

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

 
 

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