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A. Anderluh, T. Hofmaier, E. Klotzsch, O. Kudlacek, T. Stockner, H. Sitte, G. Schütz:
"Direct PIP₂ binding mediates stable oligomer formation of the serotonin transporter";
Nature Communications, 8 (2017), 140891 - 140899.

The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic
cleft and thereby terminates serotonergic signalling. We have previously found by singlemolecule
microscopy that SERT forms stable higher-order oligomers of differing stoichiometry
at the plasma membrane of living cells. Here, we report that SERToligomer assembly at
the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized
by rapid exchange of subunits between different oligomers, and by a concentration
dependence of the degree of oligomerization. After trafficking to the plasma membrane,
however, the SERT stoichiometry is fixed. Stabilization of the oligomeric SERT complexes is
mediated by the direct binding to phosphoinositide phosphatidylinositol-4,5-biphosphate
(PIP2). The observed spatial decoupling of oligomer formation from the site of oligomer
operation provides cells with the ability to define protein quaternary structures independent
of protein density at the cell surface.