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Publications in Scientific Journals:

A. Das, O. Kudlacek, F. Baumgart, K. Jaentsch, T. Stockner, H. Sitte, G. Schütz:
"Dopamine transporter forms stable dimers in the live cell plasma membrane in a phosphatidylinositol-4,5-bisphosphate independent manner";
Journal of Biological Chemistry, 294 (2019), 5632 - 5642.



English abstract:
The human dopamine transporter (hDAT) regulates the level
of the neurotransmitter dopamine (DA) in the synaptic cleft and
recycles DA for storage in the presynaptic vesicular pool. Many
neurotransmitter transporters exist as oligomers, but the physiological
role of oligomerization remains unclear; for example, it
has been speculated to be a prerequisite for amphetamine-induced
release and protein trafficking. Previous studies point to
an oligomeric quaternary structure of hDAT; however, the exact
stoichiometry and the fraction of co-existing oligomeric states
are not known. Here, we used single-molecule brightness analysis
to quantify the degree of oligomerization of heterologously
expressed hDAT fused to monomeric GFP (mGFP-hDAT) in
Chinese hamster ovary (CHO) cells. We observed that monomers
and dimers of mGFP-hDAT co-exist and that higher-order
molecular complexes of mGFP-hDAT are absent at the
plasma membrane. The mGFP-hDAT dimers were stable over
several minutes, and the fraction of dimers was independent of
the mGFP-hDAT surface density. Furthermore, neither oxidation
nor depletion of cholesterol had any effect on the fraction of
dimers. Unlike for the human serotonin transporter (hSERT), in
which direct binding of phosphatidylinositol 4,5-bisphosphate
(PIP2) stabilized the oligomers, the stability of mGFP-hDAT
dimers was PIP2 independent.

Created from the Publication Database of the Vienna University of Technology.