ArticleNature chemical biology2014
PIP2 regulates psychostimulant behaviors through its interaction with a membrane protein.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 87 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
87 citing papers in PubMed, 130 citations in OpenAlex.
- Cell membrane cholesterol affects serotonin transporter efflux due to altered transporter oligomerization.Molecular psychiatry · 2026Article
- Kappa opioid receptor antagonism restores phosphorylation, trafficking and behavior induced by a disease-associated dopamine transporter variant.Molecular psychiatry · 2025Article
- CD9-association with PIPFEBS open bio · 2025Article
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- Dimerization and substrate recognition of human taurine transporter.Nature communications · 2025Article
- Single-Vesicle Microelectroanalysis Reveals the Role of PIP2 Phospholipid in Vesicle Opening Dynamics and Its Potential Role in Exocytosis.ACS omega · 2025Article
- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
- Drosophila as an Animal Model To Determine the Functional and Behavioral Significance of Dopamine Transporter Genetic Variations Associated with Brain Disorders.Advances in neurobiology · 2025Review
- Pathogenic variants at the N-terminal arginine residue 44 disrupt human GABA transporter 1 function: insights fromFrontiers in pharmacology · 2025Article
- Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.NPJ Parkinson's disease · 2024Article
- Article
- A Conserved Intramolecular Ion-Pair Plays a Critical but Divergent Role in Regulation of Dimerization and Transport Function among the Monoamine Transporters.International journal of molecular sciences · 2024Article
- Oligomerization of Monoamine Transporters.Sub-cellular biochemistry · 2024Review
- Electrostatic switch mechanisms of membrane protein trafficking and regulation.Biophysical reviews · 2023Review
- Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIPNature communications · 2023Article
- Syntaxin 1 SerScience advances · 2023Article
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Phosphatidylinositol 4,5-bisphosphate (PIPCommunications biology · 2022Article
- Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification.Nature communications · 2022Article
- PI(4,5)P2: signaling the plasma membrane.The Biochemical journal · 2022Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedErratum.2017
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphatidylinositol (4,5)-bisphosphate (PIP2) regulates the function of ion channels and transporters. Here, we demonstrate that PIP2 directly binds the human dopamine (DA) transporter (hDAT), a key regulator of DA homeostasis and a target of the psychostimulant amphetamine (AMPH). This binding occurs through electrostatic interactions with positively charged hDAT N-terminal residues and is shown to facilitate AMPH-induced, DAT-mediated DA efflux and the psychomotor properties of AMPH. Substitution of these residues with uncharged amino acids reduces hDAT-PIP2 interactions and AMPH-induced DA efflux without altering the hDAT physiological function of DA uptake. We evaluated the significance of this interaction in vivo using locomotion as a behavioral assay in Drosophila melanogaster. Expression of mutated hDAT with reduced PIP2 interaction in Drosophila DA neurons impairs AMPH-induced locomotion without altering basal locomotion. We present what is to our knowledge the first demonstration of how PIP2 interactions with a membrane protein can regulate the behaviors of complex organisms.
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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.