Functional coupling of serotonin and noradrenaline transporters.
Re-uptake of the neurotransmitters serotonin and noradrenaline out of the synaptic cleft is mediated by selective transporter proteins, the serotonin transporter and the noradrenaline transporter respectively. Both are integral membrane proteins that are have a high degree of homology and represent members of a larger neurotransmitter transporter superfamily. Several studies have indicated that the serotonin transporter has an an oligomeric structure. To determine whether monoamine transporters can also function in oligomeric structures in situ, we constructed a concatenate consisting of one molecule of serotonin transporter covalently linked to one molecule of noradrenaline transporter. Heterologous expression of this hybrid construct allowed us to analyse the function, i.e. transport activity, and the structure, i.e. the molecular weight of the total construct and of its single components, at the same time. We showed that serotonin-noradrenaline transporter fusion proteins are fully active and exhibit the pharmacological profile of both their individual components. These findings support the hypothesis that monoamine transporters are expressed and may function as oligomeric proteins composed of non-interacting monomers.
Horschitz
Sandra
S
Biochemical Laboratory, Central Institute of Mental Health, Mannheim, Germany.
Hummerich
René
R
Schloss
Patrick
P
D000595:Amino Acid Sequence; D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics; D001667:Binding, Competitive / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015283:Citalopram / Q000493:pharmacokinetics; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics; D015151:Immunoblotting; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000378:metabolism / Q000493:pharmacokinetics; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014316:Tritium
D000928:Antidepressive Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011993:Recombinant Fusion Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; D005473:Fluoxetine; D015283:Citalopram; D014316:Tritium; C011386:nisoxetine; D012701:Serotonin; D007099:Imipramine; D009638:Norepinephrine