Functional interchangeability of rod and cone transducin α-subunits
Open accessAbstract
Rod and cone photoreceptors use similar but distinct sets of phototransduction proteins to achieve different functional properties, suitable for their role as dim and bright light receptors, respectively. For example, rod and cone visual pigments couple to distinct variants of the heterotrimeric G protein transducin. However, the role of the structural differences between rod and cone transducin alpha subunits (Talpha) in determining the functional differences between rods and cones is unknown. To address this question, we studied the translocation and signaling properties of rod Talpha expressed in cones and cone Talpha expressed in rods in three mouse strains: rod Talpha knockout, cone Talpha GNAT2(cpfl3) mutant, and rod and cone Talpha double mutant rd17 mouse. Surprisingly, although the rod/cone Talpha are only 79% identical, exogenously expressed rod or cone Talpha localized and translocated identically to endogenous Talpha in each photoreceptor type. Moreover, exogenously expressed rod or cone Talpha rescued electroretinogram responses (ERGs) in mice lacking functional cone or rod Talpha, respectively. Ex vivo transretinal ERG and single-cell recordings from rd17 retinas treated with rod or cone Talpha showed comparable rod sensitivity and response kinetics. These results demonstrate that cone Talpha forms a functional heterotrimeric G protein complex in rods and that rod and cone Talpha couple equally well to the rod phototransduction cascade. Thus, rod and cone transducin alpha-subunits are functionally interchangeable and their signaling properties do not contribute to the intrinsic light sensitivity differences between rods and cones. Additionally, the technology used here could be adapted for any such homologue swap desired.
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Gnat1 and 2 knockout mice lack expression of rod and cone α-transducin, respectively, and exhibit loss of signal transduction through these photoreceptors.
“Gnat1 and 2 knockout mice lack expression of rod and cone α-transducin, respectively, and exhibit loss of signal transduction through these photoreceptors (Deng et al., 2009; Yao et al., 2018).”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Deng et al., 2009
The ERG results section reports no detectable rod transducin α or rod-mediated responses in rod-knockout mice, and undetectable cone-mediated responses in untreated GNAT2 cpfl3 mice. But the light-induced translocation section identifies cpfl3 as a mutation, not a knockout, and reports reduced but detectable cone transducin α expression. Thus the claim is supported for the loss of responses, but not for the asserted absence of cone protein expression. (LLM, conf=0.90)
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- Authors
- Deng, W.-T., Sakurai, K., Liu, J., Dinculescu, A., Li, J., Pang, J., Min, S.-H., Chiodo, V. A., Boye, S. L., Chang, B., Kefalov, V. J., & Hauswirth, W. W.
- Affiliations
- University of Florida (US)
- Washington University in St. Louis (US)
- Corresponding author
- Deng, Wen-Tao
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-10-20
- Volume
- 106
- Issue
- 42
- Pages
- 17681-17686
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2758286
- OpenAlex
- W2155577860
- Cited by
- 46
- References
- 27
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 8 · 2012: 5
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Karl Kirchgessner Foundation
- Research to Prevent Blindness (EY02687)
- Tufts Medical Center
- National Institutes of Health (EY02687)
- National Eye Institute (EY 08571, EY 02687, P30EY002687, P30EY008571, R01EY011123, EY-11123)
- National Institute of Neurological Disorders and Stroke (NS 36302, P01NS036302)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Keywords
- transducin alpha subunit, rod photoreceptors, cone photoreceptors, phototransduction, functional interchangeability, heterotrimeric G proteins, GNAT2
- MeSH terms
- Animals, Electroretinography, Evoked Potentials, Visual, Eye Proteins, Mice, Mutant Strains, Photic Stimulation, Recombinant Proteins, Retinal Rod Photoreceptor Cells, Retinal Cone Photoreceptor Cells, Mice, Knockout, Heterotrimeric GTP-Binding Proteins, Protein Subunits, Mice
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