Elementary response triggered by transducin in retinal rods.

Wendy W S Yue, Daniel Silverman, Xiaozhi Ren, Rikard Frederiksen, Kazumi Sakai, Takahiro Yamashita, Yoshinori Shichida, M Carter Cornwall, Jeannie Chen, King-Wai Yau

Proceedings of the National Academy of Sciences of the United States of America 2019 Mar 12

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G protein-coupled receptor (GPCR) signaling is crucial for many physiological processes. A signature of such pathways is high amplification, a concept originating from retinal rod phototransduction, whereby one photoactivated rhodopsin molecule (Rho*) was long reported to activate several hundred transducins (GT*s), each then activating a cGMP-phosphodiesterase catalytic subunit (GT*·PDE*). This high gain at the Rho*-to-GT* step has been challenged more recently, but estimates remain dispersed and rely on some nonintact rod measurements. With two independent approaches, one with an extremely inefficient mutant rhodopsin and the other with WT bleached rhodopsin, which has exceedingly weak constitutive activity in darkness, we obtained an estimate for the electrical effect from a single GT*·PDE* molecular complex in intact mouse rods. Comparing the single-GT*·PDE* effect to the WT single-photon response, both in Gcaps-/- background, gives an effective gain of only ∼12-14 GT*·PDE*s produced per Rho*. Our findings have finally dispelled the entrenched concept of very high gain at the receptor-to-G protein/effector step in GPCR systems.

Citation

Wendy W S Yue, Daniel Silverman, Xiaozhi Ren, Rikard Frederiksen, Kazumi Sakai, Takahiro Yamashita, Yoshinori Shichida, M Carter Cornwall, Jeannie Chen, King-Wai Yau. Elementary response triggered by transducin in retinal rods. Proceedings of the National Academy of Sciences of the United States of America. 2019 Mar 12;116(11):5144-5153