SLC6 transporter oligomerization

Autor: Anand Kant Das, Gerhard J. Schütz, Dino Luethi, Dániel Szöllősi, Thomas Stockner, Kumaresan Jayaraman, Maarten E. A. Reith, Harald H. Sitte
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Neurochemistry
ISSN: 1471-4159
0022-3042
Popis: Transporters of the solute carrier 6 (SLC6) family mediate the reuptake of neurotransmitters such as dopamine, norepinephrine, serotonin, GABA, and glycine. SLC6 family members are 12 transmembrane helix‐spanning proteins that operate using the transmembrane sodium gradient for transport. These transporters assume various quaternary arrangements ranging from monomers to complex stoichiometries with multiple subunits. Dopamine and serotonin transporter oligomerization has been implicated in trafficking of newly formed proteins from the endoplasmic reticulum to the plasma membrane with a pre‐fixed assembly. Once at the plasma membrane, oligomers are kept fixed in their quaternary assembly by interaction with phosphoinositides. While it remains unclear how oligomer formation precisely affects physiological transporter function, it has been shown that oligomerization supports the activity of release‐type psychostimulants. Most recently, single molecule microscopy experiments unveiled that the stoichiometry differs between individual members of the SLC6 family. The present overview summarizes our understanding of the influence of plasma membrane constituents on transporter oligomerization, describes the known interfaces between protomers and discusses open questions.
We review the current knowledge on oligomerization of the solute carrier 6 (SLC6) family, which includes the transporters for the neurotransmitters dopamine, serotonin, and GABA. Early biochemical studies suggested dimer and tetramer configurations and identified several interaction motifs. Not all interfaces could be confirmed. Oligomers seem to become defined during transporter trafficking, are dependent on the plasma membrane PIP2 content, and affect substrate efflux. Simulations are starting to contribute to our understanding of transporter oligomerization, whereas recent single molecule experiments refined the oligomeric state by finding several non‐exchanging configurations for SERT, but only monomers and dimers for DAT.
Databáze: OpenAIRE
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