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

Research output: Contribution to journalArticle

56 Citations (Scopus)

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

Fingerprint

Transducin
Light Signal Transduction
Rod Cell Outer Segment
Light
Heterotrimeric GTP-Binding Proteins
Vertebrate Photoreceptor Cells
Protein Subunits
Cell Death
Down-Regulation

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., ... 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

Transducin γ-subunit sets expression levels of α- and β-subunits and is crucial for rod viability. / Lobanova, Ekaterina S.; Finkelstein, Stella; Herrmann, Rolf; Chen, Yen Ming; Kessler, Christopher; Michaud, Norman A.; Trieu, Lynn H.; Strissel, Katherine J.; Burns, Marie E; Arshavsky, Vadim Y.

In: Journal of Neuroscience, Vol. 28, No. 13, 26.03.2008, p. 3510-3520.

Research output: Contribution to journalArticle

Lobanova, ES, Finkelstein, S, Herrmann, R, Chen, YM, Kessler, C, Michaud, NA, Trieu, LH, Strissel, KJ, Burns, ME & Arshavsky, VY 2008, 'Transducin γ-subunit sets expression levels of α- and β-subunits and is crucial for rod viability', Journal of Neuroscience, vol. 28, no. 13, pp. 3510-3520. https://doi.org/10.1523/JNEUROSCI.0338-08.2008
Lobanova, Ekaterina S. ; Finkelstein, Stella ; Herrmann, Rolf ; Chen, Yen Ming ; Kessler, Christopher ; Michaud, Norman A. ; Trieu, Lynn H. ; Strissel, Katherine J. ; Burns, Marie E ; Arshavsky, Vadim Y. / Transducin γ-subunit sets expression levels of α- and β-subunits and is crucial for rod viability. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 13. pp. 3510-3520.
@article{5293726f002b470b906b2f542ba5bba8,
title = "Transducin γ-subunit sets expression levels of α- and β-subunits and is crucial for rod viability",
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.",
keywords = "Cell death, G-proteins, Photoreceptor, Protein expression, Protein localization, Transducin",
author = "Lobanova, {Ekaterina S.} and Stella Finkelstein and Rolf Herrmann and Chen, {Yen Ming} and Christopher Kessler and Michaud, {Norman A.} and Trieu, {Lynn H.} and Strissel, {Katherine J.} and Burns, {Marie E} and Arshavsky, {Vadim Y.}",
year = "2008",
month = "3",
day = "26",
doi = "10.1523/JNEUROSCI.0338-08.2008",
language = "English (US)",
volume = "28",
pages = "3510--3520",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "13",

}

TY - JOUR

T1 - Transducin γ-subunit sets expression levels of α- and β-subunits and is crucial for rod viability

AU - Lobanova, Ekaterina S.

AU - Finkelstein, Stella

AU - Herrmann, Rolf

AU - Chen, Yen Ming

AU - Kessler, Christopher

AU - Michaud, Norman A.

AU - Trieu, Lynn H.

AU - Strissel, Katherine J.

AU - Burns, Marie E

AU - Arshavsky, Vadim Y.

PY - 2008/3/26

Y1 - 2008/3/26

N2 - 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.

AB - 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.

KW - Cell death

KW - G-proteins

KW - Photoreceptor

KW - Protein expression

KW - Protein localization

KW - Transducin

UR - http://www.scopus.com/inward/record.url?scp=41549149721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41549149721&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0338-08.2008

DO - 10.1523/JNEUROSCI.0338-08.2008

M3 - Article

VL - 28

SP - 3510

EP - 3520

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 13

ER -