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The Journal of Neuroscience, March 26, 2008, 28(13):3510-3520; doi:10.1523/JNEUROSCI.0338-08.2008

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Cellular/Molecular
Transducin -Subunit Sets Expression Levels of - and β-Subunits and Is Crucial for Rod Viability

Ekaterina S. Lobanova,¹ Stella Finkelstein,¹ Rolf Herrmann,¹ Yen-Ming Chen,² Christopher Kessler,² Norman A. Michaud,³ Lynn H. Trieu,³ Katherine J. Strissel,³ Marie E. Burns,² and Vadim Y. Arshavsky¹

¹Albert Eye Research Institute, Duke University, Durham, North Carolina 27710, ²Center for Neuroscience and Department of Ophthalmology and Vision Science, University of California Davis, Davis, California 95618, and ³Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114

Correspondence should be addressed to Vadim Y. Arshavsky, Duke University Eye Center, 5008 AERI, 2351 Erwin Road, Durham, NC 27710. Email: vadim.arshavsky{at}duke.edu

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 - and β-subunits. Here we demonstrate that the knock-out of transducin -subunit leads to a major downregulation of both - and β-subunit proteins, despite nearly normal levels of the corresponding transcripts, and fairly rapid photoreceptor degeneration. Significant fractions of the remaining - and β-subunits were mislocalized from the light-sensitive outer segment compartment of the rod. Yet, the tiny amount of the -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 -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 -subunit partner sufficiently stresses the cellular biosynthetic and/or chaperone machinery to induce cell death.

Key words: transducin; photoreceptor; G-proteins; cell death; protein expression; protein localization

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Received Sept. 13, 2007; revised Feb. 19, 2008; accepted Feb. 21, 2008.

Correspondence should be addressed to Vadim Y. Arshavsky, Duke University Eye Center, 5008 AERI, 2351 Erwin Road, Durham, NC 27710. Email: vadim.arshavsky{at}duke.edu

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