Elucidating the Mechanism Behind Sodium-Coupled Neurotransmitter Transporters by Reconstitution
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Elucidating the Mechanism Behind Sodium-Coupled Neurotransmitter Transporters by Reconstitution. / Schmidt, Solveig G.; Gether, Ulrik; Loland, Claus J.
In: Neurochemical Research, Vol. 47, 2022, p. 127–137.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Elucidating the Mechanism Behind Sodium-Coupled Neurotransmitter Transporters by Reconstitution
AU - Schmidt, Solveig G.
AU - Gether, Ulrik
AU - Loland, Claus J.
PY - 2022
Y1 - 2022
N2 - Sodium-coupled neurotransmitter transporters play a fundamental role in the termination of synaptic neurotransmission, which makes them a major drug target. The reconstitution of these secondary active transporters into liposomes has shed light on their molecular transport mechanisms. From the earliest days of the reconstitution technique up to today's single-molecule studies, insights from live functioning transporters have been indispensable for our understanding of their physiological impact. The two classes of sodium-coupled neurotransmitter transporters, the neurotransmitter: sodium symporters and the excitatory amino acid transporters, have vastly different molecular structures, but complementary proteoliposome studies have sought to unravel their ion-dependence and transport kinetics. Furthermore, reconstitution experiments have been used on both protein classes to investigate the role of e.g. the lipid environment, of posttranslational modifications, and of specific amino acid residues in transport. Techniques that allow the detection of transport at a single-vesicle resolution have been developed, and single-molecule studies have started to reveal single transporter kinetics, which will expand our understanding of how transport across the membrane is facilitated at protein level. Here, we review a selection of the results and applications where the reconstitution of the two classes of neurotransmitter transporters has been instrumental.
AB - Sodium-coupled neurotransmitter transporters play a fundamental role in the termination of synaptic neurotransmission, which makes them a major drug target. The reconstitution of these secondary active transporters into liposomes has shed light on their molecular transport mechanisms. From the earliest days of the reconstitution technique up to today's single-molecule studies, insights from live functioning transporters have been indispensable for our understanding of their physiological impact. The two classes of sodium-coupled neurotransmitter transporters, the neurotransmitter: sodium symporters and the excitatory amino acid transporters, have vastly different molecular structures, but complementary proteoliposome studies have sought to unravel their ion-dependence and transport kinetics. Furthermore, reconstitution experiments have been used on both protein classes to investigate the role of e.g. the lipid environment, of posttranslational modifications, and of specific amino acid residues in transport. Techniques that allow the detection of transport at a single-vesicle resolution have been developed, and single-molecule studies have started to reveal single transporter kinetics, which will expand our understanding of how transport across the membrane is facilitated at protein level. Here, we review a selection of the results and applications where the reconstitution of the two classes of neurotransmitter transporters has been instrumental.
KW - Neurotransmitter transporters
KW - Proteoliposomes
KW - Reconstitution
KW - Membrane transport
KW - Secondary active transporters
KW - AMINOBUTYRIC-ACID TRANSPORTER
KW - GLUTAMATE TRANSPORTER
KW - DOPAMINE TRANSPORTER
KW - PARTIAL-PURIFICATION
KW - GLYCINE TRANSPORTER
KW - RAT-BRAIN
KW - MEMBRANE
KW - HOMOLOG
KW - NA+
KW - BINDING
U2 - 10.1007/s11064-021-03413-y
DO - 10.1007/s11064-021-03413-y
M3 - Journal article
C2 - 34347265
VL - 47
SP - 127
EP - 137
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
ER -
ID: 276155847