Functional consequences of truncating/substituting the bopamine transporter carboxyl terminus

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National Library of Canada , Ottawa
SeriesCanadian theses = -- Thèses canadiennes
The Physical Object
Pagination2 microfiches : negative. --
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Open LibraryOL16037873M
ISBN 100612126277

Dopamine signaling is initiated by release of dopamine from the presynaptic neuron cell, and its duration and intensity are regulated primarily by the reuptake of dopamine back into the dopaminergic neurons by the plasma membrane dopamine transporter (DAT).

Description Functional consequences of truncating/substituting the bopamine transporter carboxyl terminus PDF

1 DAT belongs to the family of Na + /Cl--dependent plasma membrane neurotransmitter. In this study, we examined the role of the carboxyl terminus of SERT in trafficking to the plasma membrane.

5-HT uptake activity was used to measure the effects of systematic deletions or alanine. Background. The dopamine transporter (DAT) is a presynaptic plasma protein found on dopaminergic nerve terminals that terminates dopamine signaling by rapidly sequestering dopamine released into the synaptic cleft [1,2].DAT belongs to a family of Na+/Cl- dependent transporters with several other neurotransmitter transporters, including norepinephrine, serotonin, GABA, and glycine transporters Cited by:   The dopamine transporter (DAT) plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron.

Previous studies have revealed that the DAT carboxyl terminus (DAT-CT) can directly interact with other cellular proteins and regulate DAT function and trafficking.

Here, we have identified that carboxypeptidase E (CPE), a prohormone processing Cited by: Truncation of the carboxyl-terminal tail and site-point mutagenesis of this part of the DAT molecule demonstrated the critical role of the carboxyl-terminus in the ER export of DAT [25, 26].

For instance, deletion of the last three residues LKV, which constitute a PDZ domain binding motif, resulted in inefficient plasma membrane expression of Cited by: ing site at the carboxyl terminus of showed that PICK-1 interacts with the C-terminus of the dopamine transporter DAT and this This work aims to study the functional consequences of.

The dopamine transporter (DAT) 1 belongs to a large family of Na + /Cl −-dependent plasma membrane transporters that also includes the closely related norepinephrine and serotonin transporters (NET and SERT, respectively), and carriers for GABA, glycine, proline, taurine, and the central nervous system, DAT mediates the re-uptake of released dopamine (DA) from the synaptic cleft.

Mapping the interaction interface for snapin/dopamine transporter (DAT) complex.

Details Functional consequences of truncating/substituting the bopamine transporter carboxyl terminus FB2

(a, b) Schematic representations of the carboxyl tail of DAT (DAT-CT) in yeast 2-hybrid assays (Y2H). The potential for the mechanism of these effects to involve the N-terminus is supported by yeast two-hybrid and fusion protein studies showing in vitro syn 1A interactions with the transporter N.

In fact, if the entire carboxyl terminus is truncated, GAT1 is also retained. Perego et al. showed that deletion of 36 amino acids from the carboxyl terminus of GAT1 did not affect membrane targeting and polarized sorting of the transporter in MDCK cells.

The authors concluded that the major part of the GAT1 carboxyl terminus was dispensable. For example, in mutant human dopamine transporter in which the C-terminus is truncated or substituted, both cocaine and CFT inhibit dopamine uptake with a K i similar to that in wild-type, while their binding affinities are at least four to fivefolds lower than those in wild-type Lee et al., a, Lee et al., b.

Truncation of the C terminus by more than 16 amino acids abrogates transport of 5-HT and binding of the inhibitor [ 3 H]-CIT by SERT. HEK cells (4 10 6 cells) were transiently transfected with. The dopamine transporter is an obligatory target of cocaine and amphetamine, as these psychostimulants have no effect on locomotor activity or dopamine.

Introduction. The dopamine transporter (DAT) 4 is a member of the solute carrier 6 (SLC6) protein family. The main physiological role of DAT (SLC6A3) is to clear catecholamines (i.e. dopamine and norepinephrine) from the synaptic cleft to achieve rapid termination of operates in relay with the cytosolic vesicular monoamine transporter to.

Introduction. Dopamine is a catecholamine neurotransmitter involved in the regulation of a variety of functions including cognition, voluntary movement, mood, sleep, learning, motivation and reward (Salamone and Correa, ; Schultz, ; Tye et al., ).The dopamine transporter (DAT) is a transmembrane protein that regulates extracellular dopamine levels through reuptake of the released.

Multiple molecular determinants in the carboxyl terminus regulate dopamine transporter export from endoplasmic reticulum. J Biol Chem – [Google Scholar] Navarro A, Encinar JA, López-Méndez B, Aguado-Llera D, Prieto J, Gómez J et al (). Mutation of Ser and Cys in Snapin modulates protein structure and stability.

to the dopamine transporter (DAT)andblock its effects (1). This "cocaine substitute" strategy is based on the goodcor-relation found between the affinities ofcocaine and cocaine like drugsforthe DATandtheirreinforcingeffects (2, 3) and the fact that the "high" is associated with the fast uptake of.

1. Introduction. Dopamine is an evolutionarily ancient catecholamine present in most eukaryotes (Callier et al., ).In many animals, dopamine plays an essential role as a modulatory neurotransmitter in many behavioral and decision-making processes, such as aggression, sexual behavior, reward, learning, and memory (Dalley & Everitt, ).The dopamine transporter (DAT).

Dopamine transporter (aka. dopamine active transporter; DAT) was first described by Iversen and colleagues in and cloned 20 years later by Giros and coworkers. DAT, a 12 transmembrane-spanning protein, is a symporter coupled to Na + /Cl − encoded on chromosome 5 (5p) and is ∼64 kbp long containing 15 coding exons.

The dopamine transporter (DAT) is a member of the neurotransmitter:sodium symporter (NSS) family of proteins belonging to the solute carrier 6 (SLC6) family that performs the reuptake of dopamine from the synaptic cleft into the presynaptic nerve required for neuronal signaling [].The essential role of DAT, and of its closely related homologs — the serotonin and norepinephrine.

The extended carboxyl terminus of the A 2A-adenosine receptor is known to engage several proteins other than those canonically involved in signalling by GPCRs (i.e., G proteins, G protein-coupled receptor kinases/GRKs, arrestins).The list includes the deubiquinating enzyme USP4, α-actinin, the guanine nucleotide exchange factor for ARF6 ARNO, translin-X-associated protein, calmodulin.

Syn1A binds to the distal N terminus of DAT and conditions that reduce its levels or prevent its interaction with the transporter lead to multiple effects including increased uptake and channel activity and decreased efflux and transporter phosphorylat 30, These findings are consistent with Syn1A functioning to suppress transport and.

Amphetamine (AMPH) elicits its behavioral effects by acting on the dopamine (DA) transporter (DAT) to induce DA efflux into the synaptic cleft. We previously demonstrated that a human DAT construct in which the first 22 amino acids were truncated was not phosphorylated by activation of protein kinase C, in contrast to wild-type (WT) DAT, which.

DOI: /M2J39J Corpus ID: Mechanisms Regulating the Dopamine Transporter and Their Impact on Behavior @inproceedings{SweeneyMechanismsRT, title={Mechanisms Regulating the Dopamine Transporter and Their Impact on Behavior}, author={Carolyn G.

Sweeney}, year={} }. Dopamine transporter deficiency syndrome is caused by mutations in the SLC6A3 gene. This gene provides instructions for making a protein called the dopamine transporter. This protein is embedded in the membrane of certain nerve cells (neurons) in the brain, where it transports a molecule called dopamine into the ne is a chemical messenger (neurotransmitter) that relays signals from.

Dopamine transporter (DAT) availability was assessed with PET and [11 C]PE2I as a marker of presynaptic dopamine function, and reward-related neural response was.

Bjerggaard, C. et al. Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions.

Regulatory elements of rat dopamine transporter N- and C-terminal domains. A 3D model of the rat dopamine (DA) transporter (DAT) based on the Aquifex aeolicus LeuT transporter was generated using PyMol (Schro¨dinger, LLC), with TM helices shown as barrels and light shading indicating semitransparent Connolly surfaces.

Abstract: The neuronal dopamine transporter/uptake site can be covalently labeled with the photoaffinity probe 1‐(2‐[bis‐(4‐fluorophenyl)methoxy]ethyl)‐4‐[2‐(4‐azido‐3‐[ I]iodophenyl)ethyl]piperazine ([ I]FAPP) and visualized following sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography.

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Upon photolysis, [ I]FAPP specifically incorporated. Adam Hill Last Modified Date: J The dopamine transporter is a type of protein that actively transports the neurotransmitter dopamine within nerve synapses. When dopamine is moved from a synapse into a neuron, it is the dopamine transporter that is mostly responsible for performing this doing this, it effectively terminates the dopamine signal being.

The neurotransmitter DA controls many functions including movement, cognition, mood, and reward. The availability of DA in the brain is modulated by DAT, a plasma membrane protein that actively translocates released transmitter from the extracellular space into the presynaptic neuron.

DAT is a target for addictive drugs including cocaine, amphetamine (AMPH), and methamphetamine (METH), and for.The dopamine transporter (DAT) is situated in the plasma membrane of the dopaminergic neurons where it mediates reuptake of dopamine from the synaptic cleft into the pre‐synaptic nerve terminus.

In this way, DAT plays a key role in terminating dopaminergic signalling and in maintaining a releasable pool of dopamine.SUMMARY: The functional imaging technique most widely used in European clinics to differentiate a true parkinsonian syndrome from vascular parkinsonism, drug-induced changes, or essential tremor is dopamine-transporter SPECT.

This technique commonly reports dopamine-transporter function, with decreasing striatal uptake demonstrating increasingly severe disease.