A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter. / Rickhag, Karl Mattias; Hansen, Freja Herborg; Sørensen, Gunnar; Strandfelt, Kristine Nørgaard; Andresen, Bjørn; Gotfryd, Kamil; Madsen, Kenneth L; Vestergaard-Klewe, Ib; Ammendrup-Johnsen, Ina; Eriksen, Jacob; Newman, Amy H; Füchtbauer, Ernst-Martin; Gomeza, Jesus; Woldbye, David P D; Wörtwein, Gitta; Gether, Ulrik.

In: Nature Communications, Vol. 4, 1580, 2013, p. 1-13.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Rickhag, KM, Hansen, FH, Sørensen, G, Strandfelt, KN, Andresen, B, Gotfryd, K, Madsen, KL, Vestergaard-Klewe, I, Ammendrup-Johnsen, I, Eriksen, J, Newman, AH, Füchtbauer, E-M, Gomeza, J, Woldbye, DPD, Wörtwein, G & Gether, U 2013, 'A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter', Nature Communications, vol. 4, 1580, pp. 1-13. https://doi.org/10.1038/ncomms2568

APA

Rickhag, K. M., Hansen, F. H., Sørensen, G., Strandfelt, K. N., Andresen, B., Gotfryd, K., ... Gether, U. (2013). A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter. Nature Communications, 4, 1-13. [1580]. https://doi.org/10.1038/ncomms2568

Vancouver

Rickhag KM, Hansen FH, Sørensen G, Strandfelt KN, Andresen B, Gotfryd K et al. A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter. Nature Communications. 2013;4:1-13. 1580. https://doi.org/10.1038/ncomms2568

Author

Rickhag, Karl Mattias ; Hansen, Freja Herborg ; Sørensen, Gunnar ; Strandfelt, Kristine Nørgaard ; Andresen, Bjørn ; Gotfryd, Kamil ; Madsen, Kenneth L ; Vestergaard-Klewe, Ib ; Ammendrup-Johnsen, Ina ; Eriksen, Jacob ; Newman, Amy H ; Füchtbauer, Ernst-Martin ; Gomeza, Jesus ; Woldbye, David P D ; Wörtwein, Gitta ; Gether, Ulrik. / A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter. In: Nature Communications. 2013 ; Vol. 4. pp. 1-13.

Bibtex

@article{f057619192994e5a936362a2f1744f02,
title = "A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter",
abstract = "The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter+Ala) are characterized by dramatic loss of dopamine transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization. In dopamine transporter-AAA neurons, but not in wild-type neurons, surface levels are rescued in part by expression of a dominant-negative dynamin mutation (K44A). Our findings suggest that PDZ-domain interactions are critical for synaptic distribution of dopamine transporter in vivo and thereby for proper maintenance of dopamine homoeostasis.",
author = "Rickhag, {Karl Mattias} and Hansen, {Freja Herborg} and Gunnar S{\o}rensen and Strandfelt, {Kristine N{\o}rgaard} and Bj{\o}rn Andresen and Kamil Gotfryd and Madsen, {Kenneth L} and Ib Vestergaard-Klewe and Ina Ammendrup-Johnsen and Jacob Eriksen and Newman, {Amy H} and Ernst-Martin F{\"u}chtbauer and Jesus Gomeza and Woldbye, {David P D} and Gitta W{\"o}rtwein and Ulrik Gether",
year = "2013",
doi = "10.1038/ncomms2568",
language = "English",
volume = "4",
pages = "1--13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter

AU - Rickhag, Karl Mattias

AU - Hansen, Freja Herborg

AU - Sørensen, Gunnar

AU - Strandfelt, Kristine Nørgaard

AU - Andresen, Bjørn

AU - Gotfryd, Kamil

AU - Madsen, Kenneth L

AU - Vestergaard-Klewe, Ib

AU - Ammendrup-Johnsen, Ina

AU - Eriksen, Jacob

AU - Newman, Amy H

AU - Füchtbauer, Ernst-Martin

AU - Gomeza, Jesus

AU - Woldbye, David P D

AU - Wörtwein, Gitta

AU - Gether, Ulrik

PY - 2013

Y1 - 2013

N2 - The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter+Ala) are characterized by dramatic loss of dopamine transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization. In dopamine transporter-AAA neurons, but not in wild-type neurons, surface levels are rescued in part by expression of a dominant-negative dynamin mutation (K44A). Our findings suggest that PDZ-domain interactions are critical for synaptic distribution of dopamine transporter in vivo and thereby for proper maintenance of dopamine homoeostasis.

AB - The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter+Ala) are characterized by dramatic loss of dopamine transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization. In dopamine transporter-AAA neurons, but not in wild-type neurons, surface levels are rescued in part by expression of a dominant-negative dynamin mutation (K44A). Our findings suggest that PDZ-domain interactions are critical for synaptic distribution of dopamine transporter in vivo and thereby for proper maintenance of dopamine homoeostasis.

U2 - 10.1038/ncomms2568

DO - 10.1038/ncomms2568

M3 - Journal article

C2 - 23481388

VL - 4

SP - 1

EP - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 1580

ER -

ID: 45487632