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

Huai Wei Huang, Jaehoon Chung, Pedro M. Domingos, Hyung Don Ryoo

Research output: Contribution to journalArticle

4 Citations (Scopus)
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Abstract

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 folding-defective 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. Folding-defective mutant rhodopsins undergo degradation in photoreceptors, but the underlying mechanism was unclear. Huang et al. identify highroad as a factor required for mutant Drosophila Rhodopsin-1 degradation. Loss of highroad accelerates retinal degeneration caused by mutant Rhodopsin-1, and highroad expression is dependent on retinoids.

Original languageEnglish
Pages (from-to)1384-1391
Number of pages8
JournalCell Reports
Volume22
Issue number6
DOIs
Publication statusPublished - 6 Feb 2018

Keywords

  • carboxypetidase
  • gene expression
  • ninaE
  • retinal degeneration
  • retinoic acid
  • retinoid
  • Rhodopsin-1

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