Expression Atlas of the Deubiquitinating Enzymes in the Adult Mouse Retina, Their Evolutionary Diversification and Phenotypic Roles

PLoS One. 2016 Mar 2;11(3):e0150364. doi: 10.1371/journal.pone.0150364. eCollection 2016.

Abstract

Ubiquitination is a relevant cell regulatory mechanism to determine protein fate and function. Most data has focused on the role of ubiquitin as a tag molecule to target substrates to proteasome degradation, and on its impact in the control of cell cycle, protein homeostasis and cancer. Only recently, systematic assays have pointed to the relevance of the ubiquitin pathway in the development and differentiation of tissues and organs, and its implication in hereditary diseases. Moreover, although the activity and composition of ubiquitin ligases has been largely addressed, the role of the deubiquitinating enzymes (DUBs) in specific tissues, such as the retina, remains mainly unknown. In this work, we undertook a systematic analysis of the transcriptional levels of DUB genes in the adult mouse retina by RT-qPCR and analyzed the expression pattern by in situ hybridization and fluorescent immunohistochemistry, thus providing a unique spatial reference map of retinal DUB expression. We also performed a systematic phylogenetic analysis to understand the origin and the presence/absence of DUB genes in the genomes of diverse animal taxa that represent most of the known animal diversity. The expression landscape obtained supports the potential subfunctionalization of paralogs in those families that expanded in vertebrates. Overall, our results constitute a reference framework for further characterization of the DUB roles in the retina and suggest new candidates for inherited retinal disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Inbred C57BL
  • Phylogeny
  • Retina / enzymology*
  • Retina / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ubiquitination*

Grant support

This study was supported by grants BFU2010-15656 (MICINN) and SAF2013-49069-C2-1-R (MINECO) to G.M., and 2014SGR-0932 (Generalitat de Catalunya) grant (BFU-2011-23434) from Ministerio de Economía y Competitividad (MINECO) and co-funded by the Fondo Europeo de Desarrollo regional (FEDER) to I.R-T. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.