Cargando…

highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models

Rhodopsins require retinoid chromophores for their function. In vertebrates, retinoids also serve as signaling molecules, but whether these molecules similarly regulate gene expression in Drosophila remains unclear. Here, we report the identification of a retinoid-inducible gene in Drosophila, highr...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Huai-Wei, Brown, Brian, Chung, Jaehoon, Domingos, Pedro M., Ryoo, Hyung Don
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832065/
https://www.ncbi.nlm.nih.gov/pubmed/29425495
http://dx.doi.org/10.1016/j.celrep.2018.01.032
_version_ 1783303255299719168
author Huang, Huai-Wei
Brown, Brian
Chung, Jaehoon
Domingos, Pedro M.
Ryoo, Hyung Don
author_facet Huang, Huai-Wei
Brown, Brian
Chung, Jaehoon
Domingos, Pedro M.
Ryoo, Hyung Don
author_sort Huang, Huai-Wei
collection PubMed
description Rhodopsins require retinoid chromophores for their function. In vertebrates, retinoids also serve as signaling molecules, but whether these molecules similarly regulate gene expression in Drosophila remains unclear. Here, we report the identification of a retinoid-inducible gene in Drosophila, highroad, which is required for photoreceptors to clear foldingdefective mutant Rhodopsin-1 proteins. Specifically, knockdown or genetic deletion of highroad blocks the degradation of folding-defective Rhodopsin-1 mutant, ninaE(G69D). Moreover, loss of highroad accelerates the age-related retinal degeneration phenotype of ninaE(G69D) mutants. Elevated highroad transcript levels are detected in ninaE(G69D) flies, and interestingly, deprivation of retinoids in the fly diet blocks this effect. Consistently, mutations in the retinoid transporter, santa maria, impairs the induction of highroad in ninaE(G69D) flies. In cultured S2 cells, highroad expression is induced by retinoic acid treatment. These results indicate that cellular quality-control mechanisms against misfolded Rhodopsin-1 involve regulation of gene expression by retinoids.
format Online
Article
Text
id pubmed-5832065
institution National Center for Biotechnology Information
language English
publishDate 2018
record_format MEDLINE/PubMed
spelling pubmed-58320652018-03-01 highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models Huang, Huai-Wei Brown, Brian Chung, Jaehoon Domingos, Pedro M. Ryoo, Hyung Don Cell Rep Article Rhodopsins require retinoid chromophores for their function. In vertebrates, retinoids also serve as signaling molecules, but whether these molecules similarly regulate gene expression in Drosophila remains unclear. Here, we report the identification of a retinoid-inducible gene in Drosophila, highroad, which is required for photoreceptors to clear foldingdefective mutant Rhodopsin-1 proteins. Specifically, knockdown or genetic deletion of highroad blocks the degradation of folding-defective Rhodopsin-1 mutant, ninaE(G69D). Moreover, loss of highroad accelerates the age-related retinal degeneration phenotype of ninaE(G69D) mutants. Elevated highroad transcript levels are detected in ninaE(G69D) flies, and interestingly, deprivation of retinoids in the fly diet blocks this effect. Consistently, mutations in the retinoid transporter, santa maria, impairs the induction of highroad in ninaE(G69D) flies. In cultured S2 cells, highroad expression is induced by retinoic acid treatment. These results indicate that cellular quality-control mechanisms against misfolded Rhodopsin-1 involve regulation of gene expression by retinoids. 2018-02-06 /pmc/articles/PMC5832065/ /pubmed/29425495 http://dx.doi.org/10.1016/j.celrep.2018.01.032 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Huang, Huai-Wei
Brown, Brian
Chung, Jaehoon
Domingos, Pedro M.
Ryoo, Hyung Don
highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models
title highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models
title_full highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models
title_fullStr highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models
title_full_unstemmed highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models
title_short highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models
title_sort highroad is a carboxypetidase induced by retinoids to clear mutant rhodopsin-1 in drosophila retinitis pigmentosa models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832065/
https://www.ncbi.nlm.nih.gov/pubmed/29425495
http://dx.doi.org/10.1016/j.celrep.2018.01.032
work_keys_str_mv AT huanghuaiwei highroadisacarboxypetidaseinducedbyretinoidstoclearmutantrhodopsin1indrosophilaretinitispigmentosamodels
AT brownbrian highroadisacarboxypetidaseinducedbyretinoidstoclearmutantrhodopsin1indrosophilaretinitispigmentosamodels
AT chungjaehoon highroadisacarboxypetidaseinducedbyretinoidstoclearmutantrhodopsin1indrosophilaretinitispigmentosamodels
AT domingospedrom highroadisacarboxypetidaseinducedbyretinoidstoclearmutantrhodopsin1indrosophilaretinitispigmentosamodels
AT ryoohyungdon highroadisacarboxypetidaseinducedbyretinoidstoclearmutantrhodopsin1indrosophilaretinitispigmentosamodels