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Publication : Elementary response triggered by transducin in retinal rods.

First Author  Yue WWS Year  2019
Journal  Proc Natl Acad Sci U S A Volume  116
Issue  11 Pages  5144-5153
PubMed ID  30796193 Mgi Jnum  J:273169
Mgi Id  MGI:6283950 Doi  10.1073/pnas.1817781116
Citation  Yue WWS, et al. (2019) Elementary response triggered by transducin in retinal rods. Proc Natl Acad Sci U S A 116(11):5144-5153
abstractText  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 approximately 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.
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