ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Rab11 supports amphetamine-stimulated norepinephrine transporter trafficking.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study.PloS one · 2012Trial
- Role of Phosphorylation of Serotonin and Norepinephrine Transporters in Animal Behavior: Relevance to Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
- Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models.Nature communications · 2022Article
- Blunted Amphetamine-induced Reinforcing Behaviors and Transporter Downregulation in Knock-in Mice Carrying Alanine Mutations at Threonine-258 and Serine-259 of Norepinephrine Transporter.Journal of molecular neuroscience : MN · 2022Article
- Identification of Potential Diagnoses Based on Immune Infiltration and Autophagy Characteristics in Major Depressive Disorder.Frontiers in genetics · 2022Article
- Neurokinin-1 Antagonism Distinguishes the Role of Norepinephrine Transporter from Dopamine Transporter in Mediating Amphetamine Behaviors.Pharmacology · 2021Article
- Article
- Interference of norepinephrine transporter trafficking motif attenuates amphetamine-induced locomotor hyperactivity and conditioned place preference.Neuropharmacology · 2018Article
- CaJournal of chemical neuroanatomy · 2017Article
- Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters.Pharmacological reviews · 2016Review
- Differentiation of rodent behavioral phenotypes and methylphenidate action in sustained and flexible attention tasks.Brain research · 2016Article
- Differential Internalization Rates and Postendocytic Sorting of the Norepinephrine and Dopamine Transporters Are Controlled by Structural Elements in the N Termini.The Journal of biological chemistry · 2016Article
- Dual agonist occupancy of AT1-R-α2C-AR heterodimers results in atypical Gs-PKA signaling.Nature chemical biology · 2015Article
- The serotonin transporter undergoes constitutive internalization and is primarily sorted to late endosomes and lysosomal degradation.The Journal of biological chemistry · 2014Article
- Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function.Neurochemistry international · 2014Article
- Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population.Molecular autism · 2014Article
- Differential targeting of the dopamine transporter to recycling or degradative pathways during amphetamine- or PKC-regulated endocytosis in dopamine neurons.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Rab11-family interacting proteins define spatially and temporally distinct regions within the dynamic Rab11a-dependent recycling system.Molecular biology of the cell · 2013Article
- Regulation of monoamine transporters: Role of transporter phosphorylation.Pharmacology & therapeutics · 2011Review
- Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The norepinephrine transporter (NET) is a presynaptic plasma membrane protein that mediates reuptake of synaptically released norepinephrine. NET is also a major target for medications used for the treatment of depression, attention deficit/hyperactivity disorder, narcolepsy, and obesity. NET is regulated by numerous mechanisms, including catalytic activation and membrane trafficking. Amphetamine (AMPH), a psychostimulant and NET substrate, has also been shown to induce NET trafficking. However, neither the molecular basis nor the nature of the relevant membrane compartments of AMPH-modulated NET trafficking has been defined. Indeed, direct visualization of drug-modulated NET trafficking in neurons has yet to be demonstrated. In this study, we used a recently developed NET antibody and the presence of large presynaptic boutons in sympathetic neurons to examine basal and AMPH-modulated NET trafficking. Specifically, we establish a role for Rab11 in AMPH-induced NET trafficking. First, we found that, in cortical slices, AMPH induces a reduction in surface NET. Next, we observed AMPH-induced accumulation and colocalization of NET with Rab11a and Rab4 in presynaptic boutons of cultured neurons. Using tagged proteins, we demonstrated that NET and a truncated Rab11 effector (FIP2DeltaC2) do not redistribute in synchrony, whereas NET and wild-type Rab11a do. Analysis of various Rab11a/b mutants further demonstrates that Rab11 regulates NET trafficking. Expression of the truncated Rab11a effector (FIP2DeltaC2) attenuates endogenous Rab11 function and prevented AMPH-induced NET internalization as does GDP-locked Rab4 S22N. Our data demonstrate that AMPH leads to an increase of NET in endosomes of single boutons and varicosities in a Rab11-dependent manner.
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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.