ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Substrate-induced internalization of the high-affinity choline transporter.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. 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, 19 citations in OpenAlex.
- Differential recruitment of acetylcholine vesicle pools by electrical stimulation and KCl depolarization in cholinergic nerve terminals.FEBS letters · 2026Article
- In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention.PloS one · 2017Article
- IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro.Cellular and molecular neurobiology · 2015Article
- Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter.ACS chemical neuroscience · 2015Article
- Serotonin-induced down-regulation of cell surface serotonin transporter.Neurochemistry international · 2014Article
- Understanding transporter specificity and the discrete appearance of channel-like gating domains in transporters.Frontiers in pharmacology · 2014Review
- Methamidophos exposure during the early postnatal period of mice: immediate and late-emergent effects on the cholinergic and serotonergic systems and behavior.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Transmembrane topology and oligomeric structure of the high-affinity choline transporter.The Journal of biological chemistry · 2012Article
- Nonoisotopic assay for the presynaptic choline transporter reveals capacity for allosteric modulation of choline uptake.ACS chemical neuroscience · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholinergic neurons are endowed with a high-affinity choline uptake system for efficient synthesis of acetylcholine at the presynaptic terminals. The high-affinity choline transporter CHT1 is responsible for choline uptake, the rate-limiting step in acetylcholine synthesis. However, endogenous physiological factors that affect CHT1 expression or function and consequently regulate the acetylcholine synthesis rate are essentially unknown. Here we demonstrate that extracellular substrate decreases the cell-surface expression of CHT1 in rat brain synaptosomes, primary cultures from the basal forebrain, and mammalian cell lines transfected with CHT1. Extracellular choline rapidly decreases cell-surface CHT1 expression by accelerating its internalization, a process that is mediated by a dynamin-dependent endocytosis pathway in HEK293 cells. Specific inhibitor hemicholinium-3 decreases the constitutive internalization rate and thereby increases cell-surface CHT1 expression. We also demonstrate that the constitutive internalization of CHT1 depends on extracellular pH in cultured cells. Our results collectively suggest that the internalization of CHT1 is induced by extracellular substrate, providing a novel feedback mechanism for the regulation of acetylcholine synthesis at the cholinergic presynaptic terminals.
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