Transducin γ-subunit sets expression levels of α- and β-subunits and is crucial for rod viability

Ekaterina S. Lobanova, Stella Finkelstein, Rolf Herrmann, Yen Ming Chen, Christopher Kessler, Norman A. Michaud, Lynn H. Trieu, Katherine J. Strissel, Marie E Burns, Vadim Y. Arshavsky

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Abstract

Transducin is a prototypic heterotrimeric G-protein mediating visual signaling in vertebrate photoreceptor cells. Despite its central role in phototransduction, little is known about the mechanisms that regulate its expression and maintain approximately stoichiometric levels of the α- and βγ-subunits. Here we demonstrate that the knock-out of transducin γ-subunit leads to a major downregulation of both α- and β-subunit proteins, despite nearly normal levels of the corresponding transcripts, and fairly rapid photoreceptor degeneration. Significant fractions of the remaining α- and β-subunits were mislocalized from the light-sensitive outer segment compartment of the rod. Yet, the tiny amount of the α-subunit present in the outer segments of knock-out rods was sufficient to support light signaling, although with a markedly reduced sensitivity. These data indicate that the γ-subunit controls the expression level of the entire transducin heterotrimer and that heterotrimer formation is essential for normal transducin localization. They further suggest that the production of transducin β-subunit without its constitutive γ-subunit partner sufficiently stresses the cellular biosynthetic and/or chaperone machinery to induce cell death.

Original languageEnglish (US)
Pages (from-to)3510-3520
Number of pages11
JournalJournal of Neuroscience
Volume28
Issue number13
DOIs
StatePublished - Mar 26 2008

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Keywords

  • Cell death
  • G-proteins
  • Photoreceptor
  • Protein expression
  • Protein localization
  • Transducin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lobanova, E. S., Finkelstein, S., Herrmann, R., Chen, Y. M., Kessler, C., Michaud, N. A., Trieu, L. H., Strissel, K. J., Burns, M. E., & Arshavsky, V. Y. (2008). Transducin γ-subunit sets expression levels of α- and β-subunits and is crucial for rod viability. Journal of Neuroscience, 28(13), 3510-3520. https://doi.org/10.1523/JNEUROSCI.0338-08.2008