title: Direct PIP2binding mediates stable oligomer formation of the serotonin transporter.
abstract: The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer 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.
authors.affiliation: Institute of Applied Physics, TU Wien, Wiedner Hauptstrasse 8-10, Vienna 1040, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Anderluh
authors.affiliation: Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University Vienna, Waehringerstrasse 13A, Vienna 1090, Austria.
authors.forename: Tina
authors.initials: T
authors.lastname: Hofmaier
authors.affiliation: EMBL Australia Node in Single Molecule Science, School of Medical Sciences, ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Enrico
authors.identifier: 0000-0002-7577-9042
authors.initials: E
authors.lastname: Klotzsch
authors.affiliation: Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University Vienna, Waehringerstrasse 13A, Vienna 1090, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kudlacek
authors.affiliation: Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University Vienna, Waehringerstrasse 13A, Vienna 1090, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stockner
authors.affiliation: Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University Vienna, Waehringerstrasse 13A, Vienna 1090, Austria.
authors.forename: Harald H
authors.identifier: 0000-0002-1339-7444
authors.initials: HH
authors.lastname: Sitte
authors.affiliation: Institute of Applied Physics, TU Wien, Wiedner Hauptstrasse 8-10, Vienna 1040, Austria.
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Schütz
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004721:Endoplasmic Reticulum; D005786:Gene Expression Regulation; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D054801:Phosphoinositide Phospholipase C