ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Calcineurin interacts with the serotonin transporter C-terminus to modulate its plasma membrane expression and serotonin uptake.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
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- Co-exposure to lead, mercury, and cadmium induces neurobehavioral impairments in mice by interfering with dopaminergic and serotonergic neurotransmission in the striatum.Frontiers in public health · 2023Article
- Trends and potential human health risk of trace elements accumulated in transplanted blue mussels during restoration activities of Flekkefjord fjord (Southern Norway).Environmental monitoring and assessment · 2022Article
- Glycogen synthase kinase-3ß supports serotonin transporter function and trafficking in a phosphorylation-dependent manner.Journal of neurochemistry · 2021Article
- Proteomics-based screening of the target proteins associated with antidepressant-like effect and mechanism of nimesulide.Scientific reports · 2020Article
- Histamine Receptors Regulate the Activity, Surface Expression, and Phosphorylation of Serotonin Transporters.ACS chemical neuroscience · 2020Article
- Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut.Nature microbiology · 2019Article
- Increased 5-HT2C receptor editing predisposes to PTSD-like behaviors and alters BDNF and cytokines signaling.Translational psychiatry · 2019Article
- Multifaceted Regulations of the Serotonin Transporter: Impact on Antidepressant Response.Frontiers in neuroscience · 2019Review
- A Functional Role for the Epigenetic Regulator ING1 in Activity-induced Gene Expression in Primary Cortical Neurons.Neuroscience · 2018Article
- Dopamine Transporter Amino and Carboxyl Termini Synergistically Contribute to Substrate and Inhibitor Affinities.The Journal of biological chemistry · 2017Article
- Translational Identification of Transcriptional Signatures of Major Depression and Antidepressant Response.Frontiers in molecular neuroscience · 2017Article
- Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters.Pharmacological reviews · 2016Review
- Akt-mediated regulation of antidepressant-sensitive serotonin transporter function, cell-surface expression and phosphorylation.The Biochemical journal · 2015Article
- Calcium dependent interaction of calmodulin with the GlyT1 C-terminus.Neurochemical research · 2014Article
- A cytosolic relay of heat shock proteins HSP70-1A and HSP90β monitors the folding trajectory of the serotonin transporter.The Journal of biological chemistry · 2014Article
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Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeostasis of serotonergic transmission critically depends on the rate of serotonin reuptake via its plasma membrane transporter (SERT). SERT activity is tightly regulated by multiple mechanisms, including physical association with intracellular proteins and post-translational modifications, such as phosphorylation, but these mechanisms remain partially understood. Here, we show that SERT C-terminal domain recruits both the catalytic and regulatory subunits of the Ca(2+)-activated protein phosphatase calcineurin (CaN) and that the physical association of SERT with CaN is promoted by CaN activity. Coexpression of constitutively active CaN with SERT increases SERT cell surface expression and 5-HT uptake in HEK-293 cells. It also prevents the reduction of 5-HT uptake induced by an acute treatment of cells with the protein kinase C activator β-PMA and concomitantly decreases PMA-elicited SERT phosphorylation. In addition, constitutive activation of CaN in vivo favors 5-HT uptake in the adult mouse brain, whereas CaN inhibition reduces cerebral 5-HT uptake. Constitutive activation of CaN also decreases immobility in the forced swim test, indicative of an antidepressant-like effect of CaN. These results identify CaN as an important regulator of SERT activity in the adult brain and provide a novel molecular substrate of clinical interest for the understanding of increased risk of mood disorders in transplanted patients treated with immunosuppressive CaN inhibitors.
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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.