Elementary response triggered by transducin in retinal rods

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cyclic GMP / metabolism
  • GTP-Binding Protein alpha Subunits / metabolism
  • Light Signal Transduction
  • Mice, Transgenic
  • Mutation / genetics
  • Phosphoric Diester Hydrolases / metabolism
  • Photons
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Rhodopsin / chemistry
  • Rhodopsin / metabolism
  • Transducin / metabolism*

Substances

  • GTP-Binding Protein alpha Subunits
  • Gnat1 protein, mouse
  • Rhodopsin
  • Phosphoric Diester Hydrolases
  • Transducin
  • Cyclic GMP