ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Regulation of HCN channel surface expression by a novel C-terminal protein-protein interaction.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 212 citations in OpenAlex.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HCN2-Associated Neurodevelopmental Disorders: Data from Patients and Xenopus Cell Models.Annals of neurology · 2025Article
- Schizophrenia-associated 22q11.2 deletion elevates striatal acetylcholine and disrupts thalamostriatal projections to produce amotivation in mice.bioRxiv : the preprint server for biology · 2025Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.eLife · 2024Article
- LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.bioRxiv : the preprint server for biology · 2024Article
- cAMP-mediated upregulation of HCN channels in VTA dopamine neurons promotes cocaine reinforcement.Molecular psychiatry · 2023Article
- Activation of metabotropic glutamate receptor 1 regulates hippocampal CA1 region excitability in rats with status epilepticus by suppressing the HCN1 channel.Neural regeneration research · 2023Article
- Effect of ivabradine on cognitive functions of rats with scopolamine-induced dementia.Scientific reports · 2022Article
- Glucocorticoid-glucocorticoid receptor-HCN1 channels reduce neuronal excitability in dorsal hippocampal CA1 neurons.Molecular psychiatry · 2022Article
- Discovery of a small-molecule inhibitor of the TRIP8b-HCN interaction with efficacy in neurons.The Journal of biological chemistry · 2022Article
- Effects of Axonal Demyelination, Inflammatory Cytokines and Divalent Cation Chelators on Thalamic HCN Channels and Oscillatory Bursting.International journal of molecular sciences · 2022Article
- Validation of the binding stoichiometry between HCN channels and their neuronal regulator TRIP8b by single molecule measurements.Frontiers in physiology · 2022Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Two Pex5 Proteins With Different Cargo Specificity Are Critical for Peroxisome Function in Ustilago maydis.Frontiers in cell and developmental biology · 2022Article
- Changes in peripheral HCN2 channels during persistent inflammation.Channels (Austin, Tex.) · 2021Article
- Hippocampal cAMP regulates HCN channel function on two time scales with differential effects on animal behavior.Science translational medicine · 2021Article
- IProgress in biophysics and molecular biology · 2021Review
- Gating movements and ion permeation in HCN4 pacemaker channels.Molecular cell · 2021Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperpolarization-activated cation currents (I(h)) are carried by channels encoded by a family of four genes (HCN1-4) that are differentially expressed within the brain in specific cellular and subcellular compartments. HCN1 shows a high level of expression in apical dendrites of cortical pyramidal neurons and in presynaptic terminals of cerebellar basket cells, structures with a high density of I(h). Expression of I(h) is also regulated by neuronal activity. To isolate proteins that may control HCN channel expression or function, we performed yeast two-hybrid screens using the C-terminal cytoplasmic tails of the HCN proteins as bait. We identified a brain-specific protein, which has been previously termed TRIP8b (for TPR-containing Rab8b interacting protein) and PEX5Rp (for Pex5p-related protein), that specifically interacts with all four HCN channels through a conserved sequence in their C-terminal tails. In situ hybridization and immunohistochemistry show that TRIP8b and HCN1 are colocalized, particularly within dendritic arbors of hippocampal CA1 and neocortical layer V pyramidal neurons. The dendritic expression of TRIP8b in layer V pyramidal neurons is disrupted after deletion of HCN1 through homologous recombination, demonstrating a key in vivo interaction between HCN1 and TRIP8b. TRIP8b dramatically alters the trafficking of HCN channels heterologously expressed in Xenopus oocytes and human embryonic kidney 293 cells, causing a specific decrease in surface expression of HCN protein and I(h) density, with a pronounced intracellular accumulation of HCN protein that is colocalized in discrete cytoplasmic clusters with TRIP8b. Finally, TRIP8b expression in cultured pyramidal neurons markedly decreases native I(h) density. These data suggest a possible role for TRIP8b in regulating HCN channel density in the plasma membrane.
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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.