ArticleBrain : a journal of neurology2023
IQGAP1 promotes chronic pain by regulating the trafficking and sensitization of TRPA1 channels.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- TRPM2 is a direct pain transducer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TRPA1 promotes overactive bladder progression by activating the NLRP3 inflammasome and driving pyroptosis.Cell death & disease · 2026Article
- Transcriptome Analysis of Non-coding RNAs and mRNAs in the Dorsal Root Ganglion of Peripheral Nerve Injury-Induced Neuropathic Pain.Biochemical genetics · 2026Article
- Neuroimmune Regulation by TRPM2 Channels.Cells · 2026Review
- The scaffold protein IQGAP1 regulates the epithelial NaThe Journal of biological chemistry · 2025Article
- Conditioned medium from painful non-NF2 schwannomatosis tumors increases pain behaviors in mice.Scientific reports · 2025Article
- IQGAP1: cross-disease target via receptor-pathway networks.Frontiers in oncology · 2025Review
- Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.International journal of molecular sciences · 2024Review
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
TRPA1 channels have been implicated in mechanical and cold hypersensitivity in chronic pain. But how TRPA1 mediates this process is unclear. Here we show that IQ motif containing GTPase activating protein 1 is responsible using a combination of biochemical, molecular, Ca2+ imaging and behavioural approaches. TRPA1 and IQ motif containing GTPase activating protein 1 bind to each other and are highly colocalized in sensory dorsal root ganglia neurons in mice. The expression of IQ motif containing GTPase activating protein 1 but not TRPA1 is increased in chronic inflammatory and neuropathic pain. However, TRPA1 undergoes increased trafficking to the membrane of dorsal root ganglia neurons catalysed by the small GTPase Cdc42 associated with IQ motif containing GTPase activating protein 1, leading to functional sensitization of the channel. Activation of protein kinase A is also sufficient to evoke TRPA1 trafficking and sensitization. All these responses are, however, completely prevented in the absence of IQ motif containing GTPase activating protein 1. Concordantly, deletion of IQ motif containing GTPase activating protein 1 markedly reduces mechanical and cold hypersensitivity in chronic inflammatory and neuropathic pain in mice. IQ motif containing GTPase activating protein 1 thus promotes chronic pain by coupling the trafficking and signalling machineries to TRPA1 channels.
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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.