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Proc Natl Acad Sci U S A. 2019 Mar 12;116(11):5144-5153. doi: 10.1073/pnas.1817781116. Epub 2019 Feb 22.

Elementary response triggered by transducin in retinal rods.

Author information

1
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
2
Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
3
Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
4
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118.
5
Department of Biophysics, Kyoto University, Kyoto 606-8502, Japan.
6
Research Organization for Science and Technology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
7
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089.
8
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089.
9
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205; kwyau@jhmi.edu.
10
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Abstract

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.

KEYWORDS:

G protein-coupled receptor; apo-opsin; rhodopsin; rod phototransduction; signal amplification

PMID:
30796193
PMCID:
PMC6421417
DOI:
10.1073/pnas.1817781116
[Indexed for MEDLINE]
Free PMC Article

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