ArticleProceedings of the National Academy of Sciences of the United States of America2002
Internalization and recycling of 5-HT2A receptors activated by serotonin and protein kinase C-mediated mechanisms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 102 citations in OpenAlex.
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- Serotonin 2A receptor attenuates psoriatic inflammation by suppressing IL-23 secretion in monocyte-derived Langerhans cells.Nature communications · 2025Article
- The evolution of N, N-Dimethyltryptamine: from metabolic pathways to brain connectivity.Psychopharmacology · 2025Review
- Hippocampal Zkscan4 confers resilience to chronic stress-induced depression-like behaviors.Science advances · 2025Article
- Raphe and ventrolateral medulla proteomics in sudden unexplained death in childhood with febrile seizure history.Acta neuropathologica · 2024Article
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics.Molecular psychiatry · 2023Review
- Effects of Electron Radiation on Serotonin Signaling and Reactivity of Rat Gastric Smooth Muscle.Toxics · 2023Article
- Dynamics and Patterning of 5-Hydroxytryptamine 2 Subtype Receptors in JC Polyomavirus Entry.Viruses · 2022Article
- Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3.Molecular psychiatry · 2022Article
- Serotonin: an overlooked regulator of endocytosis and endosomal sorting?Biology open · 2022Article
- Ginsenoside Re Protects against Serotonergic Behaviors Evoked by 2,5-Dimethoxy-4-iodo-amphetamine in Mice via Inhibition of PKCδ-Mediated Mitochondrial Dysfunction.International journal of molecular sciences · 2021Article
- Protective effects of antidepressant citalopram against abnormal APP processing and amyloid beta-induced mitochondrial dynamics, biogenesis, mitophagy and synaptic toxicities in Alzheimer's disease.Human molecular genetics · 2021Article
- PACAP-PAC1 Signaling Regulates Serotonin 2A Receptor Internalization.Frontiers in endocrinology · 2021Article
- Serotonin Receptor and Transporter Endocytosis Is an Important Factor in the Cellular Basis of Depression and Anxiety.Frontiers in cellular neuroscience · 2021Article
- Serotonin 2A (5-HTScientific reports · 2020Article
- Mania- and anxiety-like behavior and impaired maternal care in female diacylglycerol kinase eta and iota double knockout mice.Genes, brain, and behavior · 2020Article
- Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons.iScience · 2020Article
- 14-3-3 signal adaptor and scaffold proteins mediate GPCR trafficking.Scientific reports · 2019Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serotonin (5-HT), a major neurotransmitter, has a large number of G protein-coupled receptors in mammals. On activation by exposure to their ligand, 5-HT(2) receptor subtypes increase IP(3) levels and undergo desensitization and internalization. To visualize the receptor in cells during these processes, we have constructed a 5-HT(2A)-enhanced GFP (SR2-GFP) fusion receptor. We show that this fusion receptor undergoes internalization on exposure to its natural ligand, 5-HT. Because 5-HT(2A) receptors activate the phospholipase C pathway, we studied the effect of protein kinase C (PKC) on the internalization process and found that activation of PKC by its specific activator phorbol 12-myristate 13-acetate, in the absence of 5-HT, leads to internalization of the receptor. Moreover, inhibition of PKC by its inhibitor sphingosine in the presence of 5-HT prevents the internalization process, suggesting that activation of PKC is sufficient and necessary for the internalization of 5-HT(2A) receptors. We also show that SR2-GFP recycles back to the plasma membrane after 5-HT-dependent internalization, suggesting a mechanism for resensitization. In addition, receptors that have been internalized on addition of phorbol 12-myristate 13-acetate in the absence of 5-HT also recycle to the surface, with a time course similar to that seen after activation of the receptors by 5-HT. Our study suggests that 5-HT(2A) receptors internalize and return to the surface after both serotonin- and PKC-mediated processes. This study reveals a role for PKC in receptor internalization and also shows that 5-HT(2A) receptors are recycled.
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