ArticleThe Journal of biological chemistry2014
Filamin A promotes dynamin-dependent internalization of hyperpolarization-activated cyclic nucleotide-gated type 1 (HCN1) channels and restricts Ih in hippocampal neurons.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- Phosphoproteomics unveils the signaling dynamics in neuronal cells stimulated with insulin and insulin-like growth factors.Cell communication and signaling : CCS · 2025Article
- Hyperpolarization-activated cyclic nucleotide-gated channels and epilepsy: genetics, circuits, and treatments.Frontiers in neurology · 2025Review
- Secretome of the Olfactory Ensheathing Cells Influences the Behavior of Neural Stem Cells.International journal of molecular sciences · 2024Article
- ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Identification of HCN1 as a 14-3-3 client.PloS one · 2022Article
- HCN Channel Phosphorylation Sites Mapped by Mass Spectrometry in Human Epilepsy Patients and in an Animal Model of Temporal Lobe Epilepsy.Neuroscience · 2021Article
- Hemizygous FLNA variant in West syndrome without periventricular nodular heterotopia.Human genome variation · 2020Article
- Fragile X mental retardation protein modulates somatic D-type KJournal of neurophysiology · 2020Article
- The structure and function of TRIP8b, an auxiliary subunit of hyperpolarization-activated cyclic-nucleotide gated channels.Channels (Austin, Tex.) · 2020Review
- Altering integrin engagement regulates membrane localization of KJournal of cell science · 2019Article
- International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.Pharmacological reviews · 2018Review
- Loss of HCN2 leads to delayed gastrointestinal motility and reduced energy intake in mice.PloS one · 2018Article
- Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels in Epilepsy.Cold Spring Harbor perspectives in medicine · 2016Review
- Filamin A Is Involved in HIV-1 Vpu-mediated Evasion of Host Restriction by Modulating Tetherin Expression.The Journal of biological chemistry · 2016Article
- An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors.Investigative ophthalmology & visual science · 2015Article
- Article
- Dysfunctional HCN ion channels in neurological diseases.Frontiers in cellular neuroscience · 2015Article
- Filamin C: a novel component of the KCNE2 interactome during hypoxia.Cardiovascular journal of AfricaArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The actin-binding protein filamin A (FLNa) regulates neuronal migration during development, yet its roles in the mature brain remain largely obscure. Here, we probed the effects of FLNa on the regulation of ion channels that influence neuronal properties. We focused on the HCN1 channels that conduct Ih, a hyperpolarization-activated current crucial for shaping intrinsic neuronal properties. Whereas regulation of HCN1 channels by FLNa has been observed in melanoma cell lines, its physiological relevance to neuronal function and the underlying cellular pathways that govern this regulation remain unknown. Using a combination of mutational, pharmacological, and imaging approaches, we find here that FLNa facilitates a selective and reversible dynamin-dependent internalization of HCN1 channels in HEK293 cells. This internalization is accompanied by a redistribution of HCN1 channels on the cell surface, by accumulation of the channels in endosomal compartments, and by reduced Ih density. In hippocampal neurons, expression of a truncated dominant-negative FLNa enhances the expression of native HCN1. Furthermore, acute abrogation of HCN1-FLNa interaction in neurons, with the use of decoy peptides that mimic the FLNa-binding domain of HCN1, abolishes the punctate distribution of HCN1 channels in neuronal cell bodies, augments endogenous Ih, and enhances the rebound-response ("voltage-sag") of the neuronal membrane to transient hyperpolarizing events. Together, these results support a major function of FLNa in modulating ion channel abundance and membrane trafficking in neurons, thereby shaping their biophysical properties and function.
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