ArticleThe Journal of biological chemistry2011
Myristoylation of cGMP-dependent protein kinase dictates isoform specificity for serotonin transporter regulation.
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 12 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.Journal of affective disorders · 2015Pooled it
- Nitrergic Signaling Mediation of Neurobehavioral Responses to Stress in Zebrafish.Journal of neurochemistry · 2025Review
- Prenatal Opioid and Alcohol Exposures: Association with Altered Placental Serotonin Transporter Structure and/or Expression.International journal of molecular sciences · 2024Article
- Article
- A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus.Molecular psychiatry · 2018Article
- Aggressive behaviours, food deprivation and theRoyal Society open science · 2017Article
- The DrosophilaCognitive development · 2017Article
- Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters.Pharmacological reviews · 2016Review
- Control of serotonin transporter phosphorylation by conformational state.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Role of nitric oxide in the behavioral and neurochemical effects of IB-MECA in zebrafish.Psychopharmacology · 2015Article
- Cyclic GMP-dependent stimulation of serotonin transport does not involve direct transporter phosphorylation by cGMP-dependent protein kinase.The Journal of biological chemistry · 2012Article
- Colocalization and regulated physical association of presynaptic serotonin transporters with A₃ adenosine receptors.Molecular pharmacology · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
By transporting serotonin (5-HT) into neurons and other cells, serotonin transporter (SERT) modulates the action of 5-HT at cell surface receptors. SERT itself is modulated by several processes, including the cGMP signaling pathway. Activation of SERT by cGMP requires the cGMP-dependent protein kinase (PKG). Here we show that in HeLa cells lacking endogenous PKG, expression of PKGIα or PKGIβ was required for 8-bromoguanosine-3',5'-cyclic monophosphate (8-Br-cGMP) to stimulate SERT phosphorylation and 5-HT influx. Catalytically inactive PKG mutants and wild-type PKGII did not support this stimulation. However, a mutant PKGII (G2A) that was not myristoylated substituted for functional PKGI, suggesting that myristoylation and subsequent membrane association blocked productive interaction with SERT. PKG also influenced SERT expression and localization. PKGI isoforms increased total and cell surface SERT levels, and PKGII decreased cell surface SERT without altering total expression. Remarkably, these changes did not require 8-Br-cGMP or functional kinase activity and were also observed with a SERT mutant resistant to activation by PKG. Both PKGIα and PKGIβ formed detergent-stable complexes with SERT, and this association did not require catalytic activity. The nonmyristoylated PKGII G2A mutant stimulated SERT expression similar to PKGI isoforms. These results suggest multiple mechanisms by which PKG can modulate SERT and demonstrate that the functional difference between PKG isoforms results from myristoylation of PKGII.
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Registered trials
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