Transducin gamma-subunit sets expression levels of alpha- and beta-subunits and is crucial for rod viability.
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 alpha- and betagamma-subunits. Here we demonstrate that the knock-out of transducin gamma-subunit leads to a major downregulation of both alpha- and beta-subunit proteins, despite nearly normal levels of the corresponding transcripts, and fairly rapid photoreceptor degeneration. Significant fractions of the remaining alpha- and beta-subunits were mislocalized from the light-sensitive outer segment compartment of the rod. Yet, the tiny amount of the alpha-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 gamma-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 beta-subunit without its constitutive gamma-subunit partner sufficiently stresses the cellular biosynthetic and/or chaperone machinery to induce cell death.
Lobanova
Ekaterina S
ES
Albert Eye Research Institute, Duke University, Durham, North Carolina 27710, USA.
Finkelstein
Stella
S
Herrmann
Rolf
R
Chen
Yen-Ming
YM
Kessler
Christopher
C
Michaud
Norman A
NA
Trieu
Lynn H
LH
Strissel
Katherine J
KJ
Burns
Marie E
ME
Arshavsky
Vadim Y
VY
D000818:Animals; D000831:Animals, Newborn; D003623:Dark Adaptation / Q000502:physiology; D004596:Electroretinography; D005074:Evoked Potentials, Visual / Q000502:physiology; D005136:Eye Proteins; D020555:GTP-Binding Protein Regulators / Q000172:deficiency; D015870:Gene Expression / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018408:Patch-Clamp Techniques / Q000379:methods; D010750:Phosphoproteins / Q000172:deficiency; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000648:ultrastructure; D015293:Transducin / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology*
D005136:Eye Proteins; D020555:GTP-Binding Protein Regulators; D010750:Phosphoproteins; C065631:phosducin; D015293:Transducin