Pias3-dependent SUMOylation controls mammalian cone photoreceptor differentiation

Nat Neurosci. 2010 Sep;13(9):1059-65. doi: 10.1038/nn.2618. Epub 2010 Aug 22.


Selective expression of retinal cone opsin genes is essential for color vision, but the mechanism mediating this process is poorly understood. Both vertebrate rod and medium wavelength-sensitive (M) cone photoreceptors differentiate by repression of a short wavelength-sensitive (S) cone differentiation program. We found that Pias3 acts in mouse cone photoreceptors to activate expression of M opsin and repress expression of S opsin, with the transcription factors Trbeta2 and Rxrgamma mediating preferential expression of Pias3 in M cones. Finally, we observed that Pias3 directly regulated M and S cone opsin expression by modulating the cone-enriched transcription factors Rxrgamma, Roralpha and Trbeta1. Our results indicate that Pias3-dependent SUMOylation of photoreceptor-specific transcription factors is a common mechanism that controls both rod and cone photoreceptor subtype specification, regulating distinct molecular targets in the two cell types.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / physiology*
  • Cone Opsins / genetics
  • Cone Opsins / metabolism
  • Gene Expression Regulation / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurogenesis / physiology*
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • Retinal Cone Photoreceptor Cells / cytology*
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Rod Photoreceptor Cells / cytology
  • Retinal Rod Photoreceptor Cells / physiology
  • Sequence Homology, Nucleic Acid
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Cone Opsins
  • Pias3 protein, mouse
  • Protein Inhibitors of Activated STAT
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors