Functional interchangeability of rod and cone transducin alpha-subunits.
Evoked-Potentials-Visual, Eye-Proteins, Heterotrimeric-GTP-Binding-Proteins, Mice-Knockout, Mice-Mutant-Strains, Photic-Stimulation, Protein-Subunits, Recombinant-Proteins, Retinal-Cone-Photoreceptor-Cells, Retinal-Rod-Photoreceptor-Cells
Proc Natl Acad Sci U S A 2009 Oct; 106(42):17681-6.
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.
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.; and Hauswirth, W W., "Functional interchangeability of rod and cone transducin alpha-subunits." (2009). Faculty Research 2000 - 2009. 2061.