| First Author | Kolesnikov AV | Year | 2022 |
| Journal | PLoS One | Volume | 17 |
| Issue | 8 | Pages | e0272506 |
| PubMed ID | 35939447 | Mgi Jnum | J:330789 |
| Mgi Id | MGI:7329461 | Doi | 10.1371/journal.pone.0272506 |
| Citation | Kolesnikov AV, et al. (2022) Regulation of rod photoreceptor function by farnesylated G-protein gamma-subunits. PLoS One 17(8):e0272506 |
| abstractText | Heterotrimeric G-protein transducin, Gt, is a key signal transducer and amplifier in retinal rod and cone photoreceptor cells. Despite similar subunit composition, close amino acid identity, and identical posttranslational farnesylation of their Ggamma subunits, rods and cones rely on unique Ggamma1 (Gngt1) and Ggammac (Gngt2) isoforms, respectively. The only other farnesylated G-protein gamma-subunit, Ggamma11 (Gng11), is expressed in multiple tissues but not retina. To determine whether Ggamma1 regulates uniquely rod phototransduction, we generated transgenic rods expressing Ggamma1, Ggammac, or Ggamma11 in Ggamma1-deficient mice and analyzed their properties. Immunohistochemistry and Western blotting demonstrated the robust expression of each transgenic Ggamma in rod cells and restoration of Galphat1 expression, which is greatly reduced in Ggamma1-deficient rods. Electroretinography showed restoration of visual function in all three transgenic Ggamma1-deficient lines. Recordings from individual transgenic rods showed that photosensitivity impaired in Ggamma1-deficient rods was also fully restored. In all dark-adapted transgenic lines, Galphat1 was targeted to the outer segments, reversing its diffuse localization found in Ggamma1-deficient rods. Bright illumination triggered Galphat1 translocation from the rod outer to inner segments in all three transgenic strains. However, Galphat1 translocation in Ggamma11 transgenic mice occurred at significantly dimmer background light. Consistent with this, transretinal ERG recordings revealed gradual response recovery in moderate background illumination in Ggamma11 transgenic mice but not in Ggamma1 controls. Thus, while farnesylated Ggamma subunits are functionally active and largely interchangeable in supporting rod phototransduction, replacement of retina-specific Ggamma isoforms by the ubiquitous Ggamma11 affects the ability of rods to adapt to background light. |
