Modulation of dopamine transporter function through protein interactions.

  • 165 Pages
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  • English
The Physical Object
Pagination165 leaves.
ID Numbers
Open LibraryOL19084643M
ISBN 100612690660

This modulation occurs largely through redistribution of the transporter protein at the cell surface rather than changes in intrinsic transport activity.

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In PC12 cells stably transfected with DAT, PKC activation increases the rate of transporter internalization while decreasing the rate of transporter recycling to the plasma membrane (Loder Cited by: Results from recent studies suggest that the D2Rs increases DAT surface expression and thereby dopamine reuptake capacity either through a direct interaction with the transporter (Bolan et al.

) or by receptor activation and subsequent stimulation of MAPK/ERK signalling pathway (Lee et al. Through coupling to Gi, D2Rs exerts an Cited by: The rat dopamine transporter (rDAT), plentiful in the presynaptic plasma membrane of dopaminergic terminals, Modulation of dopamine transporter function through protein interactions.

book 12 transmembrane domains and belongs to the Na + /Cl ‐ ‐dependent transporter family (22; 1; 10).The principal function of the dopamine transporter (DAT) is to control the synaptic levels of dopamine by reuptake of dopamine into presynaptic by: Keywords: human dopamine transporter, repurposable drugs, amphetamine, orphenadrine cocaine, drug modulation mechanism.

Citation: Cheng MH, Block E, Hu F, Cobanoglu MC, Sorkin A and Bahar I () Insights into the modulation of dopamine transporter function by amphetamine, orphenadrine, and cocaine binding. by: () /j‐x Abstract The dopamine transporter (DAT) plays a key role in regulating dopaminergic signalling in the brain by mediating rapid clearance of dop Regulation of dopamine transporter function by protein‐protein interactions: new discoveries and methodological challenges - Eriksen - - Journal of Cited by:   The plasma membrane-associated GTPase Rin interacts with the dopamine transporter and is required for protein kinase C-regulated dopamine transporter trafficking.

J Neuro –, doi. The dopamine transporter has been identified from brains of various species and from Caenorhabditis elegans (for references see Table 1).A transporter with neuronal dopamine transporter properties and a partial cDNA clone has also been characterized from the African green monkey kidney (COS) cell line (Sugamori et al., ).The mammalian dopamine transporters exhibit high sequence.

J. Eriksen, et tion of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges J. Eriksen J, Jorgensen TN, Gether U ().

Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges. J Neurochem 27– CAS. Through interactions with these transporters, the neuronal cytoskeleton, and pre-synaptic scaffolding proteins, α-synuclein, β-synuclein, and γ-synuclein modulate trafficking, expression and function of monoamine transporters at the cell surface, thus playing a central role in regulating monoamine re-uptake.

Andrea Varrone, Christer Halldin, in Imaging of the Human Brain in Health and Disease, Abstract. The dopamine transporter (DAT) is a transmembrane protein that is responsible for the reuptake of dopamine (DA) from the synaptic cleft and for the termination of dopaminergic transmission.

The DAT is a target of several drugs, including psychostimulants, such as amphetamine and cocaine, and. Modulation of Dopamine Transporter Function by Tamoxifen by Sarah Rose Mikelman A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Pharmacology) in the University of Michigan Doctoral Committee: Professor.

Dopamine modulation of neuronal activity during memory tasks identifies a non-linear inverted-U shaped function. Both the dopamine transporter (DAT) and dopamine D2 receptors (encoded by DRD2) critically regulate dopamine signaling in the striatum and in prefrontal cortex during er, in vitro studies have demonstrated that DAT and D2 proteins reciprocally regulate.

The Caenorhabditis elegans (C. elegans) dopamine (DA) transporter (DAT-1) regulates DA signaling through efficient DA reuptake following synaptic release.

In addition to its DA transport function, DAT-1 generates detectible DA-gated currents that may influence neuronal excitability. Previously, we provided evidence that single Cl-channel events underlie DAT-1 currents.

Conditions Related To Dopamine Transporter Function. When something goes wrong with the dopamine transporter, the dopamine builds up between the synapses of the brain. This excess dopamine can cause several problems, both physical and psychological. Dopamine Beta Hydroxylase Deficiency.

Dopamine beta-hydroxylase deficiency can happen in infancy. Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood.

Here, we identified the synaptic vesicle protein. Dopamine Transporter–Protein Interactions. DAT interacts directly and indirectly with numerous proteins (in addition to the kinases and ubiquitinases already discussed) that are important in regulating localization and function (for review, see Eriksen et al., b).

DAT localization to intracellular locales or plasma membrane domains. 1. Introduction. Like most members of the Na + /Cl −-dependent carrier family, the serotonin transporter (SERT) is expressed on the plasma membrane, where it catalyzes the uptake of serotonin (Torres et al., ; Kristensen et al., ).SERT serves as an important regulator of the signal amplitude and duration at the serotonergic synapses that ultimately drive serotonin-associated.

All clinically approved drugs targeting the plasmalemmal transporters for dopamine, norepinephrine, and serotonin act either as competitive uptake inhibitors or as amphetamine-like releasers. Monoamine transporter (MAT) ligands that allosterically affect MAT-mediated substrate uptake, release, or both were recently discovered.

Their modes of action have not yet been explained in a unified. A concentration dependent modulation of this protein on the trafficking of DAT has been suggested in mice, and the direct interaction between the two proteins has been demonstrated in vitro [32, 37].

α and γ-synucleins have been found upregulated after a high dose cocaine regimen in the dorsal striatum of rats. Cumulative evidence suggest that the HIV-1 Tat protein exerts the neurotoxicity through interaction with human dopamine transporter (hDAT) in the CNS.

modulation of the DAT function and. Abstract. D 3 dopamine receptors are expressed by dopamine neurons and are implicated in the modulation of presynaptic dopamine neurotransmission. The mechanisms underlying this modulation remain ill defined. The dopamine transporter, which terminates dopamine transmission via reuptake of released neurotransmitter, is regulated by receptor- and second messenger-linked signaling pathways.

In addition, normal uptake function through the dopamine transporter was unaltered by the PKCβ inhibitors, as measured in rat synaptosomes. Our results support the utility of using PKCβ. Amine transporter (PubMed, PubMed, PubMed). Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals (By similarity).

Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity). Computational modeling of human dopamine transporter structures, mechanism and its interaction with HIV-1 transactivator of transcription.

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Future Med Chem [Google Scholar] Yuan Y, Quizon PM, Sun WL, Yao J, Zhu J, Zhan CG. Role of Histidine of Human Dopamine Transporter in Molecular Interaction with HIV-1 Tat and Dopamine Uptake.

The modulation of DAT by a-Syn is well described in vitro and is mediated through direct protein-protein interactions between the NAC (non-amyloid-b component) region of a-Syn and the final   Through interactions with these transporters, the neuronal cytoskeleton, and pre-synaptic scaffolding proteins, alpha-synuclein, beta-synuclein, and gamma-synuclein modulate trafficking, expression and function of monoamine transporters at the cell surface, thus playing a central role in regulating monoamine re-uptake.

One of the key presynaptic components involved in regulating dopaminergic tone is the dopamine transporter (DAT). Here, we report that the DAT is also regulated by the dopamine D2 receptor through a direct protein-protein interaction involving the DAT amino-terminus and.

The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into the cytosol, other transporters sequester the dopamine into vesicles for storage and later release.

Dopamine reuptake via DAT provides the primary mechanism through which dopamine is cleared. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves.

Modulation of neurotransmission by the monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is critical for normal nervous system function. Precise temporal and spatial control of this signaling in mediated in large part by the actions of monoamine transporters (DAT, NET, and SERT, respectively).

Description Modulation of dopamine transporter function through protein interactions. FB2

These transporters act to recapture their respective neurotransmitters after. Thus, in both dopamine clearance and dopamine release assays performed in vivo, nicotine effects on dopamine transporter function and dopamine efflux are sustained across a 60 min period.

Ghosheh et al () demonstrated that peak nicotine brain levels occur by 5 min after peripheral injection and that the half-life of nicotine in rat brain is.

Uptake through the Dopamine Transporter (DAT) is the primary mechanism of terminating dopamine signaling within the brain, thus playing an essential role in neuronal homeostasis. Deregulation of DAT function has been linked to several neurological and psychiatric disorders including ADHD, schizophrenia, Parkinson’s disease, and drug addiction.

Over the last 15 years, several .