ArticleJournal of cell science2013
CALHM1 controls the Ca²⁺-dependent MEK, ERK, RSK and MSK signaling cascade in neurons.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Genetic association of CALHM1 rs2986017 polymorphism with risk of Alzheimer's disease: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2016Pooled it
- CALHM5 deficiency alleviates aortic aneurysm by regulating smooth muscle calcium homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biology, function and structure of the calcium homeostasis modulator family.The Journal of physiology · 2025Review
- Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red.Nature communications · 2023Article
- Distal extracellular teneurin region (teneurin C-terminal associated peptide; TCAP) possesses independent intracellular calcium regulating actions,Biochemistry and biophysics reports · 2022Article
- Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites ofBrain sciences · 2022Article
- Human CALHM5: Insight in large pore lipid gating ATP channel and associated neurological pathologies.Molecular and cellular biochemistry · 2021Review
- Proteomic and Transcriptomic Analyses Reveal Pathological Changes in the Entorhinal Cortex Region that Correlate Well with Dysregulation of Ion Transport in Patients with Alzheimer's Disease.Molecular neurobiology · 2021Article
- The Polysite Pharmacology of TREK KAdvances in experimental medicine and biology · 2021Article
- Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment.International journal of molecular sciences · 2020Review
- Calcium-Handling Defects and Neurodegenerative Disease.Cold Spring Harbor perspectives in biology · 2020Review
- Polynuclear Ruthenium Amines Inhibit KCell chemical biology · 2020Article
- Article
- CALHM1/CALHM3 channel is intrinsically sorted to the basolateral membrane of epithelial cells including taste cells.Scientific reports · 2019Article
- Drug Development for Alzheimer's Disease: Microglia Induced Neuroinflammation as a Target?International journal of molecular sciences · 2019Review
- Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex.Science signaling · 2018Article
- Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors.Molecular psychiatry · 2018Article
- ATP Release Channels.International journal of molecular sciences · 2018Review
- Post-translational palmitoylation controls the voltage gating and lipid raft association of the CALHM1 channel.The Journal of physiology · 2017Article
- Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Calcium homeostasis modulator 1 (CALHM1) is a Ca(2+) channel controlling neuronal excitability and potentially involved in the pathogenesis of Alzheimer's disease (AD). Although strong evidence indicates that CALHM1 is required for neuronal electrical activity, its role in intracellular Ca(2+) signaling remains unknown. In the present study, we show that in hippocampal HT-22 cells, CALHM1 expression led to a robust and relatively selective activation of the Ca(2+)-sensing kinases ERK1/2. CALHM1 also triggered activation of MEK1/2, the upstream ERK1/2-activating kinases, and of RSK1/2/3 and MSK1, two downstream effectors of ERK1/2 signaling. CALHM1-mediated activation of ERK1/2 signaling was controlled by the small GTPase Ras. Pharmacological inhibition of CALHM1 permeability using Ruthenium Red, Zn(2+), and Gd(3+), or expression of the CALHM1 N140A and W114A mutants, which are deficient in mediating Ca(2+) influx, prevented the effect of CALHM1 on the MEK, ERK, RSK and MSK signaling cascade, demonstrating that CALHM1 controlled this pathway via its channel properties. Importantly, expression of CALHM1 bearing the natural P86L polymorphism, which leads to a partial loss of CALHM1 function and is associated with an earlier age at onset in AD patients, showed reduced activation of ERK1/2, RSK1/2/3, and MSK1. In line with these results obtained in transfected cells, primary cerebral neurons isolated from Calhm1 knockout mice showed significant impairments in the activation of MEK, ERK, RSK and MSK signaling. The present study identifies a previously uncharacterized mechanism of control of Ca(2+)-dependent ERK1/2 signaling in neurons, and further establishes CALHM1 as a critical ion channel for neuronal signaling and function.
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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.