G protein-coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number of downstream G protein/enzyme effector complexes. However, rod phototransduction is light-activated, whereas GPCR pathways are predominantly ligand-activated. Here, we report a detailed study of the ligand-triggered GPCR pathway in mammalian olfactory transduction, finding that an odorant-receptor molecule when (one-time) complexed with its most effective odorants produces on average much less than one downstream effector. Further experiments gave a nominal success probability of tentatively ∼10 (more conservatively, ∼10 to ∼10). This picture is potentially more generally representative of GPCR signaling than is rod phototransduction, constituting a paradigm shift.
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http://dx.doi.org/10.1073/pnas.2121225119 | DOI Listing |
Front Mol Neurosci
December 2024
Pennsylvania College of Optometry, Salus at Drexel University, Elkins Park, PA, United States.
Retinal membrane guanylyl cyclase (RetGC), regulated by guanylyl cyclase activating proteins (GCAPs) via negative calcium-feedback, is one of the most critically important enzymes in vertebrate rod and cone physiology, enabling their sensitivity to light. It was also reported that, similarly to olfactory receptor guanylyl cyclase, bicarbonate anion directly stimulates RetGC activity in photoreceptors as a novel phototransduction-linked regulating factor. We directly tested whether or not RetGC is a bicarbonate-activated enzyme using recombinant human RetGC expressed in HEK293 cells and the native RetGC in mouse retinas.
View Article and Find Full Text PDFBiochemistry
December 2024
Gavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, Irvine, California 92697, United States.
Arrestins halt signal transduction by binding to the phosphorylated C-termini of activated G protein-coupled receptors. Arrestin-1, the first subtype discovered, binds to rhodopsin in rod cells. Mutations in , the gene encoding Arrestin-1, are linked to Oguchi disease, characterized by delayed dark adaptation.
View Article and Find Full Text PDFbioRxiv
December 2024
Wake Forest University, School of Medicine, Department of Biochemistry.
Glucose-sensing ChREBP and MondoA are transcriptional factors involved in lipogenic, inflammatory, and insulin signaling pathways implicated in metabolic disorders; however, limited ocular studies have been conducted on these proteins. We aimed to investigate the potential role of ChREBP in pathogenesis of diabetic retinopathy (DR). We used diabetic human and mouse retinal cryosections analyzed by immunohistochemistry.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Retinal rods and cones underlie scotopic and photopic vision, respectively. Their pigments exhibit spontaneous isomerizations (quantal noise) in darkness due to intrinsic thermal energy. This quantal noise, albeit exceedingly low in rods, dictates the light threshold for scotopic vision.
View Article and Find Full Text PDFMicrobiol Res
November 2024
State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, PR China. Electronic address:
Light-controlled motility is advantageous for photosynthetic prokaryotes to better survive in environment with constantly changing light conditions. For cyanobacteria, light is both an energy source for photosynthesis and a stress factor. Consequently, some cyanobacteria evolved the ability to control type-IV pili (T4P)-mediated surface motility using a chemotaxis-like system in response to light signals.
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