Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity. / Lycas, Matthew D.; Ejdrup, Aske L.; Sørensen, Andreas T.; Haahr, Nicolai O.; Jørgensen, Søren H.; Guthrie, Daryl A.; Støier, Jonatan F.; Werner, Christian; Newman, Amy Hauck; Sauer, Markus; Herborg, Freja; Gether, Ulrik.

In: Cell Reports, Vol. 40, No. 13, 111431, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Lycas, MD, Ejdrup, AL, Sørensen, AT, Haahr, NO, Jørgensen, SH, Guthrie, DA, Støier, JF, Werner, C, Newman, AH, Sauer, M, Herborg, F & Gether, U 2022, 'Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity', Cell Reports, vol. 40, no. 13, 111431. https://doi.org/10.1016/j.celrep.2022.111431

APA

Lycas, M. D., Ejdrup, A. L., Sørensen, A. T., Haahr, N. O., Jørgensen, S. H., Guthrie, D. A., Støier, J. F., Werner, C., Newman, A. H., Sauer, M., Herborg, F., & Gether, U. (2022). Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity. Cell Reports, 40(13), [111431]. https://doi.org/10.1016/j.celrep.2022.111431

Vancouver

Lycas MD, Ejdrup AL, Sørensen AT, Haahr NO, Jørgensen SH, Guthrie DA et al. Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity. Cell Reports. 2022;40(13). 111431. https://doi.org/10.1016/j.celrep.2022.111431

Author

Lycas, Matthew D. ; Ejdrup, Aske L. ; Sørensen, Andreas T. ; Haahr, Nicolai O. ; Jørgensen, Søren H. ; Guthrie, Daryl A. ; Støier, Jonatan F. ; Werner, Christian ; Newman, Amy Hauck ; Sauer, Markus ; Herborg, Freja ; Gether, Ulrik. / Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity. In: Cell Reports. 2022 ; Vol. 40, No. 13.

Bibtex

@article{5fc48b77049c443e9c75317b14eeb8ce,
title = "Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity",
abstract = "The nanoscopic organization and regulation of individual molecular components in presynaptic varicosities of neurons releasing modulatory volume neurotransmitters like dopamine (DA) remain largely elusive. Here we show, by application of several super-resolution microscopy techniques to cultured neurons and mouse striatal slices, that the DA transporter (DAT), a key protein in varicosities of dopaminergic neurons, exists in the membrane in dynamic equilibrium between an inward-facing nanodomain-localized and outward-facing unclustered configuration. The balance between these configurations is inversely regulated by excitatory drive and DA D2 autoreceptor activation in a manner dependent on Ca2+ influx via N-type voltage-gated Ca2+ channels. The DAT nanodomains contain tens of transporters molecules and overlap with nanodomains of PIP2 (phosphatidylinositol-4,5-bisphosphate) but show little overlap with D2 autoreceptor, syntaxin-1, and clathrin nanodomains. The data reveal a mechanism for rapid alterations of nanoscopic DAT distribution and show a striking link of this to the conformational state of the transporter.",
keywords = "CP: Neuroscience, dopamine receptors, dopamine transporter, fluorescent cocaine analogues, nanodomains, neurotransmitter transporters, PIP2, super-resolution microscopy, synaptic architecture, volume transmission",
author = "Lycas, {Matthew D.} and Ejdrup, {Aske L.} and S{\o}rensen, {Andreas T.} and Haahr, {Nicolai O.} and J{\o}rgensen, {S{\o}ren H.} and Guthrie, {Daryl A.} and St{\o}ier, {Jonatan F.} and Christian Werner and Newman, {Amy Hauck} and Markus Sauer and Freja Herborg and Ulrik Gether",
note = "Publisher Copyright: {\textcopyright} 2022",
year = "2022",
doi = "10.1016/j.celrep.2022.111431",
language = "English",
volume = "40",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",

}

RIS

TY - JOUR

T1 - Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2 autoreceptor activity

AU - Lycas, Matthew D.

AU - Ejdrup, Aske L.

AU - Sørensen, Andreas T.

AU - Haahr, Nicolai O.

AU - Jørgensen, Søren H.

AU - Guthrie, Daryl A.

AU - Støier, Jonatan F.

AU - Werner, Christian

AU - Newman, Amy Hauck

AU - Sauer, Markus

AU - Herborg, Freja

AU - Gether, Ulrik

N1 - Publisher Copyright: © 2022

PY - 2022

Y1 - 2022

N2 - The nanoscopic organization and regulation of individual molecular components in presynaptic varicosities of neurons releasing modulatory volume neurotransmitters like dopamine (DA) remain largely elusive. Here we show, by application of several super-resolution microscopy techniques to cultured neurons and mouse striatal slices, that the DA transporter (DAT), a key protein in varicosities of dopaminergic neurons, exists in the membrane in dynamic equilibrium between an inward-facing nanodomain-localized and outward-facing unclustered configuration. The balance between these configurations is inversely regulated by excitatory drive and DA D2 autoreceptor activation in a manner dependent on Ca2+ influx via N-type voltage-gated Ca2+ channels. The DAT nanodomains contain tens of transporters molecules and overlap with nanodomains of PIP2 (phosphatidylinositol-4,5-bisphosphate) but show little overlap with D2 autoreceptor, syntaxin-1, and clathrin nanodomains. The data reveal a mechanism for rapid alterations of nanoscopic DAT distribution and show a striking link of this to the conformational state of the transporter.

AB - The nanoscopic organization and regulation of individual molecular components in presynaptic varicosities of neurons releasing modulatory volume neurotransmitters like dopamine (DA) remain largely elusive. Here we show, by application of several super-resolution microscopy techniques to cultured neurons and mouse striatal slices, that the DA transporter (DAT), a key protein in varicosities of dopaminergic neurons, exists in the membrane in dynamic equilibrium between an inward-facing nanodomain-localized and outward-facing unclustered configuration. The balance between these configurations is inversely regulated by excitatory drive and DA D2 autoreceptor activation in a manner dependent on Ca2+ influx via N-type voltage-gated Ca2+ channels. The DAT nanodomains contain tens of transporters molecules and overlap with nanodomains of PIP2 (phosphatidylinositol-4,5-bisphosphate) but show little overlap with D2 autoreceptor, syntaxin-1, and clathrin nanodomains. The data reveal a mechanism for rapid alterations of nanoscopic DAT distribution and show a striking link of this to the conformational state of the transporter.

KW - CP: Neuroscience

KW - dopamine receptors

KW - dopamine transporter

KW - fluorescent cocaine analogues

KW - nanodomains

KW - neurotransmitter transporters

KW - PIP2

KW - super-resolution microscopy

KW - synaptic architecture

KW - volume transmission

U2 - 10.1016/j.celrep.2022.111431

DO - 10.1016/j.celrep.2022.111431

M3 - Journal article

C2 - 36170827

AN - SCOPUS:85138825773

VL - 40

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 13

M1 - 111431

ER -

ID: 322283247