The carboxyl terminal mutational hotspot of the ciliary disease protein RPGRORF15 (retinitis pigmentosa GTPase regulator) is glutamylated in vivo
Document Type
Journal ArticlePublication Date
2016-04-15Keywords
CiliaGT335
Glutamylation
RPGR
Retina
Biochemistry
Eye Diseases
Genetics and Genomics
Medical Genetics
Molecular Biology
Ophthalmology
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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.Source
Biol Open. 2016 Apr 15;5(4):424-8. doi: 10.1242/bio.016816. Link to article on publisher's siteDOI
10.1242/bio.016816Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39932PubMed ID
26941104Related Resources
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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.Distribution License
http://creativecommons.org/licenses/by/3.0/ae974a485f413a2113503eed53cd6c53
10.1242/bio.016816
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Except where otherwise noted, this item's license is described as 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.</p>