ArticleProceedings of the National Academy of Sciences of the United States of America2012
G-protein-mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 97 citations in OpenAlex.
- Non-canonical pore architecture underlies constitutive gating of human retinal TRPM1.Nature communications · 2026Article
- Cryo-EM structure of TRPM1 reveals a non-canonical architecture with an inverted transmembrane domain.Nature communications · 2026Article
- Direct crosstalk between GPCRs and ion channels via G proteins.Experimental & molecular medicine · 2025Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- The architecture of invaginating rod synapses slows glutamate diffusion and shapes synaptic responses.The Journal of general physiology · 2025Article
- Defective glycosylation and ELFN1 binding of mGluR6 congenital stationary night blindness mutants.Life science alliance · 2025Article
- Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders.Biochemical Society transactions · 2024Review
- The Variety of Mechanosensitive Ion Channels in Retinal Neurons.International journal of molecular sciences · 2024Review
- TRPM channels in health and disease.Nature reviews. Nephrology · 2024Review
- Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling.International journal of molecular sciences · 2023Article
- Potentiation of neuronal activity by tonic GluD1 current in brain slices.EMBO reports · 2023Article
- A visual opsin from jellyfish enables precise temporal control of G protein signalling.Nature communications · 2023Article
- Bipolar cell targeted optogenetic gene therapy restores parallel retinal signaling and high-level vision in the degenerated retina.Communications biology · 2022Article
- Review
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- AUY922 induces retinal toxicity through attenuating TRPM1.Journal of biomedical science · 2021Article
- The structural basis for an on-off switch controlling Gβγ-mediated inhibition of TRPM3 channels.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Melatonin promotes sleep by activating the BK channel inProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Sensing through Non-Sensing Ocular Ion Channels.International journal of molecular sciences · 2020Review
- Light-Adapted Electroretinogram Differences in Autism Spectrum Disorder.Journal of autism and developmental disorders · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
ON bipolar cells are critical for the function of the ON pathway in the visual system. They express a metabotropic glutamate receptor (mGluR6) that, when activated, couples to the G(o) class of G protein. The channel that is primarily responsible for the synaptic response has been recently identified as the transient receptor potential cation channel subfamily M member 1 (TRPM1); TRPM1 is negatively coupled to the mGluR6/Go cascade such that activation of the cascade results in closure of the channel. Light indirectly opens TRPM1 by reducing transmitter release from presynaptic photoreceptors, resulting in a decrease in mGluR6 activation. Conversely, in the dark, binding of synaptic glutamate to mGluR6 inhibits TRPM1 current. Closure of TRPM1 by G-protein activation in the dark is a critical step in the process of ON bipolar cell signal transduction, but the precise pathway linking these two events is not understood. To address this question, we measured TRPM1 activity in retinal bipolar cells, in human ependymal melanocytes (HEMs) that endogenously express TRPM1, and in HEK293 cells transfected with TRPM1. Dialysis of the Gβγ subunit dimer, but not Gα(o), closed TRPM1 channels in every cell type that we tested. In addition, activation of an endogenous G-protein-coupled receptor pathway in HEK293 cells that releases Gβγ without activating Go protein also closed TRPM1 channels. These results suggest a model in which the Gβγ dimer that is released as a result of the dissociation from Gα(o) upon activation of mGluR6 closes the TRPM1 channel, perhaps via a direct interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.