Transducin β-Subunit Can Interact with Multiple G-Protein γ-Subunits to Enable Light Detection by Rod Photoreceptors.

Abstract

The heterotrimeric G-protein transducin mediates visual signaling in vertebrate photoreceptor cells. Many aspects of the function of transducin were learned from knock-out mice lacking its individual subunits. Of particular interest is the knockout of its rod-specific γ-subunit (Gγ1). Two studies using independently generated mice documented that this knockout results in a considerable >60-fold reduction in the light sensitivity of affected rods, but provided different interpretations of how the remaining α-subunit (Gαt) mediates phototransduction without its cognate Gβ1γ1-subunit partner. One study found that the light sensitivity reduction matched a corresponding reduction in Gαt content in the light-sensing rod outer segments and proposed that Gαt activation is supported by remaining Gβ1 associating with other Gγ subunits naturally expressed in photoreceptors. In contrast, the second study reported the same light sensitivity loss but a much lower, only approximately sixfold, reduction of Gαt and proposed that the light responses of these rods do not require Gβγ at all. To resolve this controversy and elucidate the mechanism driving visual signaling in Gγ1 knock-out rods, we analyzed both mouse lines side by side. We first determined that the outer segments of both mice have identical Gαt content, which is reduced ∼65-fold from the wild-type (WT) level. We further demonstrated that the remaining Gβ1 is present in a complex with endogenous Gγ2 and Gγ3 subunits and that these complexes exist in wild-type rods as well. Together, these results argue against the idea that Gαt alone supports light responses of Gγ1 knock-out rods and suggest that Gβ1γ1 is not unique in its ability to mediate vertebrate phototransduction.

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Citation

Published Version (Please cite this version)

10.1523/eneuro.0144-18.2018

Publication Info

Dexter, Paige M, Ekaterina S Lobanova, Stella Finkelstein, William J Spencer, Nikolai P Skiba and Vadim Y Arshavsky (2018). Transducin β-Subunit Can Interact with Multiple G-Protein γ-Subunits to Enable Light Detection by Rod Photoreceptors. eNeuro, 5(3). pp. ENEURO.0144-18.2018–ENEURO.0144-18.2018. 10.1523/eneuro.0144-18.2018 Retrieved from https://hdl.handle.net/10161/17214.

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Scholars@Duke

Skiba

Nikolai Petrovich Skiba

Associate Professor of Ophthalmology

My research focuses on applying mass spectrometry based proteomics to study proteins in eye tissues, cells and sub-cellular compartments to understand mechanisms of vision. An important aspect of my research is to identify proteins in different compartments of retinal photoreceptor cells, their amount and modification status at different cell states defined by the light conditions, genotype, disease etc. This information can be valuable in understanding molecular mechanisms of vision and biology of the photoreceptor cell. Another important aspect of my research is to assist basic scientist and clinicians in our department in their proteomic needs which include identification of proteins and other biomolecules in a given biological sample, detection of protein post-translational modifications and sequence variations, elucidation of protein-protein interactions and also characterization of changes in the protein concentration and composition in a biological sample at different conditions.

Arshavsky

Vadim Y Arshavsky

Helena Rubinstein Foundation Distinguished Professor of Ophthalmology

Research conducted in our laboratory is dedicated to understanding how vision is performed on the molecular level. Our most mature direction addresses the function of rod and cone photoreceptors, which are sensory neurons responsible for the detection and primary processing of information entering the eye in the form of photons. Photoreceptors respond to capturing photons by generating electrical signals transmitted to the secondary neurons in the retina and, ultimately, to the brain. Our work is dedicated to uncovering the molecular mechanisms underlying three essential photoreceptor functions: their uniquely high light-sensitivity, their ability to rapidly recover from light excitation, and their capacity to modulate light-responses upon broad variations in the intensity of ambient illumination.

Our second direction is to elucidate the cellular processes responsible for building the light-sensitive organelle of photoreceptor cells, called the outer segment, and for populating this organelle with proteins conducting visual signaling. Of particular interest is the mechanism by which outer segments form their “disc” membrane stacks providing vast membrane surfaces for effective photon capture.

Finally, we are seeking connections between understanding the basic function of rods and cones and practical, translational approaches to ameliorate the retinal degeneration caused by mutations in critical photoreceptor-specific proteins. Most importantly, we explore the link between the balance of protein synthesis and degradation in photoreceptor cells (the “proteostasis”) and the status of their health.


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