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PXD032663

PXD032663 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe dopamine transporter antiports potassium to increase the uptake of dopamine
DescriptionThe dopamine transporter facilitates dopamine reuptake from the extracellular space to terminate neurotransmission. The transporter belongs to the neurotransmitter:sodium symporter family, which includes transporters for serotonin, norepinephrine, and GABA that utilize the Na+ gradient to drive the uptake of substrate. Decades ago, it was shown that the serotonin transporter also antiports K+, but investigations of K+-coupled transport in other neurotransmitter:sodium symporters have been inconclusive. Here, we show that ligand binding to the drosophila- and human dopamine transporters are inhibited by K+, and the conformational dynamics of the drosophila dopamine transporter in K+ are divergent from the apo- and Na+-states. Furthermore, we found that K+ increased dopamine uptake by the drosophila dopamine transporter in liposomes, and visualized Na+ and K+ fluxes in single proteoliposomes using fluorescent ion indicators. Our results expand on the fundamentals of dopamine transport and prompt a reevaluation of the impact of K+ on other transporters in this pharmacologically important family.
HostingRepositoryPRIDE
AnnounceDate2022-05-20
AnnouncementXMLSubmission_2022-05-20_08:42:07.317.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKasper Rand
SpeciesList scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationListNo PTMs are included in the dataset
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-20 15:28:57ID requested
12022-05-20 08:42:08announced
Publication List
Schmidt SG, Malle MG, Nielsen AK, Bohr SS, Pugh CF, Nielsen JC, Poulsen IH, Rand KD, Hatzakis NS, Loland CJ, The dopamine transporter antiports potassium to increase the uptake of dopamine. Nat Commun, 13(1):2446(2022) [pubmed]
Keyword List
ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)
submitter keyword: MS
Membrane proteins
Mass spectroemetry
Hydrogen-deuterium exchange
Transporter
Contact List
Kasper D. Rand
contact affiliationProtein Analysis Group, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark
contact emailkasper.rand@sund.ku.dk
lab head
Kasper Rand
contact affiliationDepartment of Pharmacy, University of Copenhagen
contact emailkasper.rand@sund.ku.dk
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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