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


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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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

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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.


Vadim Y Arshavsky

Helena Rubinstein Foundation Distinguished Professor of Ophthalmology

The Biology and Pathophysiology of Vertebrate Photoreceptor Cells

Research conducted in our laboratory is dedicated to understanding how vision is performed on the molecular level. Most of our work is centered on vertebrate photoreceptor cells, which are sensory neurons responsible for light detection in the eye. Photoreceptors capture photons, produce an electrical signal, and transmit this information to the secondary neurons in the retina, and ultimately to the brain, through modulation of their synaptic release. 

The main experimental direction of our laboratory 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 supporting its structure and conducting visual signaling. Of particular interest is the mechanism by which outer segments form their “disc” membrane stacks providing vast membrane surfaces for efficient photon capture. Outer segment membranes are continuously renewed throughout the lifetime of a photoreceptor, with new discs added to the outer segment base and old discs phagocytosed at the tip by the retinal pigment epithelium. As a result, the entire mammalian outer segment is replaced with new discs over the course of 8-10 days. One of the central goals of our current studies is to elucidate the signaling pathway that acts as a “control center” to initiate the formation of each new disc with the strikingly regular frequency of approximately 80 times per day. 

Our second major research direction explores a connection between understanding the basic function of rods and cones and practical, translational ideas aiming to ameliorate retinal degeneration caused by mutations in critical photoreceptor-specific proteins. Several years ago, we found that photoreceptors bearing a broad spectrum of disease-associated mutations suffer from a common cellular stress factor, proteasomal overload, i.e. insufficient ability of the ubiquitin-proteasome system to process misfolded and/or mislocalized proteins produced in these cells. Our more recent data demonstrate that the enhancement of protein degradation machinery in these cells causes a remarkable delay in the progression of photoreceptor degeneration. We continue investigating photoreceptor proteostasis in further mechanistic depth and seek optimal strategies to employ proteasomal activation as a means to ameliorate or cure inherited blindness. 

During our studies, we explore high-end applications of mass spectrometry-based proteomics and were the first laboratory adopting several advanced proteomic approaches to vision research. Of particular significance are the applications of so-called “label-free” quantitative proteomics for simultaneous elucidation of multiple protein distributions among different compartments of the photoreceptor cells and for identification of unique protein components of various photoreceptor membranes. Using label-free proteomics, we demonstrated that a small protein PRCD (progressive rod and cone degeneration) is a unique component of photoreceptor discs and subsequently identified several novel unique components of the plasma membrane enclosing the rod outer segment. Most recently, we adopted a highly efficient and accurate methodology for simultaneous absolute quantification of several dozen proteins, termed MS Western. This method allowed us to determine the precise molar ratio amongst all major functional and structural proteins residing in the light-sensitive outer segments of photoreceptor cells.

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