Light-Induced Translocation of RGS9-1 and Gβ5L in Mouse Rod Photoreceptors

Abstract

The transducin GTPase-accelerating protein complex, which determines the photoresponse duration of photoreceptors, is composed of RGS9-1, Gβ5L and R9AP. Here we report that RGS9-1 and Gβ5L change their distribution in rods during light/dark adaptation. Upon prolonged dark adaptation, RGS9-1 and Gβ5L are primarily located in rod inner segments. But very dim-light exposure quickly translocates them to the outer segments. In contrast, their anchor protein R9AP remains in the outer segment at all times. In the dark, Gβ5L's interaction with R9AP decreases significantly and RGS9-1 is phosphorylated at S475 to a significant degree. Dim light exposure leads to quick de-phosphorylation of RGS9-1. Furthermore, after prolonged dark adaptation, RGS9-1 and transducin Gα are located in different cellular compartments. These results suggest a previously unappreciated mechanism by which prolonged dark adaptation leads to increased light sensitivity in rods by dissociating RGS9-1 from R9AP and redistributing it to rod inner segments.

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

“…The RGS9 gene has been mapped to the identical site as the retinitis pigmentosa gene on chromosome 17 (q23-24) implicating RGS9 as having involvement in degenerative retinal disease (Arshavsky and Wensel, 2013;Granneman et al, 1998;Lai et al, 2013;Sundermeier et al, 2014;Tian et al, 2013;Vincent et al, 2013;Zhang et al, 2012b;Ziccardi et al, 2012). The RGS9 gene produces two major alternatively spliced mRNAs that give rise to substantially different C-termini.…”

RGS Protein Regulation of Phototransduction

“…Given that rod photoresponse duration is controlled by transducin GAP level, it is of interest to note that RGS9-1 was recently reported to reside mainly in the inner segment under prolonged dark adaptation and move swiftly out to the outer segment upon illumination. 64 The reported translocation of RGS9-1 from inner to outer segment occurred at much dimmer illumination than those required to translocate transducin or arrestin. Interestingly, of the three components of the transducin GAP, only RGS9-1 and Gβ5-L exhibit this peculiar translocation phenomenon and the anchoring protein R9AP stays in the outer segment regardless of illumination level.…”

“…Light exposure leads to a rapid decrease in S475 phosphorylation, promoting the assembly of the ternary protein complex and translocation to outer segment. 64 This finding is somewhat at odd with the well-documented stereotypic nature of rod single-photon responses. 67 Should translocation of RGS9-1 and Gβ5-L in fact occur, one would expect the single-photon responses to have some degree of variability in recovery phase.…”

“…67 Should translocation of RGS9-1 and Gβ5-L in fact occur, one would expect the single-photon responses to have some degree of variability in recovery phase. However, should RGS9-1 translocation occur quickly, as shown in just a few minutes upon dim light exposure, 64 only the initial few recorded light responses will deviate from the ensemble responses typically collected hundreds of times every 5–10 s for a period of 30 + min during suction pipette recordings. Clearly, there is much work to be done here to solve this controversy.…”

The Emerging Role of Gβ Subunits in Human Genetic Diseases

“…Gnb5-null mouse models displayed marked neurobehavioral abnormalities, impaired gait and motor learning, hyperactivity [62][63][64][65], defective visual adaptation with perturbed development and functioning of retinal bipolar cells [127][128][129]. Moreover, targeted deletion of one or two copies of the Gnb5 gene had distinct effects on body weight and behavior in mice [62].…”