ArticleThe Journal of biological chemistry2011
Trafficking of alpha4* nicotinic receptors revealed by superecliptic phluorin: effects of a beta4 amyotrophic lateral sclerosis-associated mutation and chronic exposure to nicotine.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 55 citations in OpenAlex.
- The exocyst is an insulin-sensitive regulator of amyloid precursor protein trafficking and amyloid-beta generation in neurons.bioRxiv : the preprint server for biology · 2026Article
- Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells.Journal of visualized experiments : JoVE · 2025Article
- Simulating early steps in nicotine dependence: Pharmacokinetics, activation, and chaperoning of nicotinic receptors.Molecular pharmacology · 2025Article
- BiallelicBrain communications · 2025Article
- Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics.Biophysical journal · 2023Article
- Rare Missense Variants of the Human β4 Subunit Alter Nicotinic α3β4 Receptor Plasma Membrane Localisation.Molecules (Basel, Switzerland) · 2023Article
- Secretory defects in pediatric osteosarcoma result from downregulation of selective COPII coatomer proteins.iScience · 2022Article
- ER-GCaMP6f: An Endoplasmic Reticulum-Targeted Genetic Probe to Measure Calcium Activity in Astrocytic Processes.Analytical chemistry · 2022Article
- A novel effect of PDLIM5 in α7 nicotinic acetylcholine receptor upregulation and surface expression.Cellular and molecular life sciences : CMLS · 2022Article
- Article
- Novel Putative Positive Modulators of α4β2 nAChRs Potentiate Nicotine Reward-Related Behavior.Molecules (Basel, Switzerland) · 2021Article
- Cytisine is neuroprotective in female but not male 6-hydroxydopamine lesioned parkinsonian mice and acts in combination with 17-β-estradiol to inhibit apoptotic endoplasmic reticulum stress in dopaminergic neurons.Journal of neurochemistry · 2021Article
- Vesicular and uncoated Rab1-dependent cargo carriers facilitate ER to Golgi transport.Journal of cell science · 2020Article
- Determining the pharmacokinetics of nicotinic drugs in the endoplasmic reticulum using biosensors.The Journal of general physiology · 2019Article
- Chronic Menthol Does Not Change Stoichiometry or Functional Plasma Membrane Levels of MouseMolecular pharmacology · 2019Article
- CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors.eLife · 2018Article
- Organelle-specific single-molecule imaging of α4β2 nicotinic receptors reveals the effect of nicotine on receptor assembly and cell-surface trafficking.The Journal of biological chemistry · 2017Article
- Selective and regulated trapping of nicotinic receptor weak base ligands and relevance to smoking cessation.eLife · 2017Article
- Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking.Journal of visualized experiments : JoVE · 2017Article
- Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons.The Journal of physiology · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We employed a pH-sensitive GFP analog, superecliptic phluorin, to observe aspects of nicotinic acetylcholine receptor (nAChR) trafficking to the plasma membrane (PM) in cultured mouse cortical neurons. The experiments exploit differences in the pH among endoplasmic reticulum (ER), trafficking vesicles, and the extracellular solution. The data confirm that few α4β4 nAChRs, but many α4β2 nAChRs, remain in neutral intracellular compartments, mostly the ER. We observed fusion events between nAChR-containing vesicles and PM; these could be quantified in the dendritic processes. We also studied the β4R348C polymorphism, linked to amyotrophic lateral sclerosis (ALS). This mutation depressed fusion rates of α4β4 receptor-containing vesicles with the PM by ∼2-fold, with only a small decrease in the number of nAChRs per vesicle. The mutation also decreased the number of ER exit sites, showing that the reduced receptor insertion results from a change at an early stage in trafficking. We confirm the previous report that the mutation leads to reduced agonist-induced currents; in the cortical neurons studied, the reduction amounts to 2-3-fold. Therefore, the reduced agonist-induced currents are caused by the reduced number of α4β4-containing vesicles reaching the membrane. Chronic nicotine exposure (0.2 μM) did not alter the PM insertion frequency or trafficking behavior of α4β4-laden vesicles. In contrast, chronic nicotine substantially increased the number of α4β2-containing vesicle fusions at the PM; this stage in α4β2 nAChR up-regulation is presumably downstream from increased ER exit. Superecliptic phluorin provides a tool to monitor trafficking dynamics of nAChRs in disease and addiction.
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