ArticleJournal of cell science2015
SNX14 is a bifunctional negative regulator for neuronal 5-HT6 receptor signaling.
Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Survey of nucleotide-specific Rab GTPase interactions reveals multiple Rab effectors.bioRxiv : the preprint server for biology · 2026Article
- SNX9 family mediates βarrestin-independent GPCR endocytosis.Communications biology · 2024Article
- SNX14 inhibits autophagy via the PI3K/AKT/mTOR signaling cascade in breast cancer cells.Journal of molecular histology · 2024Article
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.Cell · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.bioRxiv : the preprint server for biology · 2024Article
- A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer.Frontiers in oncology · 2023Review
- Transmembrane Membrane Readers form a Novel Class of Proteins That Include Peripheral Phosphoinositide Recognition Domains and Viral Spikes.Membranes · 2022Review
- Structural Predictions of the SNX-RGS Proteins Suggest They Belong to a New Class of Lipid Transfer Proteins.Frontiers in cell and developmental biology · 2022Article
- Sorting Out Sorting Nexins Functions in the Nervous System in Health and Disease.Molecular neurobiology · 2021Review
- SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate.National science review · 2021Article
- SNX-PXA-RGS-PXC Subfamily of SNXs in the Regulation of Receptor-Mediated Signaling and Membrane Trafficking.International journal of molecular sciences · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- A novel genomic region on chromosome 11 associated with fearfulness in dogs.Translational psychiatry · 2020Article
- The emerging role of sorting nexins in cardiovascular diseases.Clinical science (London, England : 1979) · 2019Review
- SNX14 mutations affect endoplasmic reticulum-associated neutral lipid metabolism in autosomal recessive spinocerebellar ataxia 20.Human molecular genetics · 2018Article
- The Role of G-proteins and G-protein Regulating Proteins in Depressive Disorders.Frontiers in pharmacology · 2018Review
- RAD-Seq Reveals Patterns of Additive Polygenic Variation Caused by Spatially-Varying Selection in the American Eel (Anguilla rostrata).Genome biology and evolution · 2017Article
- Genome sequencing reveals a splice donor site mutation in the SNX14 gene associated with a novel cerebellar cortical degeneration in the Hungarian Vizsla dog breed.BMC genetics · 2016Article
- Serotonin, neural markers, and memory.Frontiers in pharmacology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
The 5-hydroxytryptamine (5-HT, also known as serotonin) subtype 6 receptor (5-HT6R, also known as HTR6) plays roles in cognition, anxiety and learning and memory disorders, yet new details concerning its regulation remain poorly understood. In this study, we found that 5-HT6R directly interacted with SNX14 and that this interaction dramatically increased internalization and degradation of 5-HT6R. Knockdown of endogenous SNX14 had the opposite effect. SNX14 is highly expressed in the brain and contains a putative regulator of G-protein signaling (RGS) domain. Although its RGS domain was found to be non-functional as a GTPase activator for Gαs, we found that it specifically bound to and sequestered Gαs, thus inhibiting downstream cAMP production. We further found that protein kinase A (PKA)-mediated phosphorylation of SNX14 inhibited its binding to Gαs and diverted SNX14 from Gαs binding to 5-HT6R binding, thus facilitating the endocytic degradation of the receptor. Therefore, our results suggest that SNX14 is a dual endogenous negative regulator in 5-HT6R-mediated signaling pathway, modulating both signaling and trafficking of 5-HT6R.
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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.