title: Membrane glycoprotein M6B interacts with the human serotonin transporter.
abstract: The serotonin transporter (SERT) belongs to a family of sodium- and chloride-dependent neurotransmitter transporters that are responsible for the active re-uptake of the neurotransmitter serotonin from the synapse. In the present study, using the yeast two-hybrid system, we identified the membrane glycoprotein M6B as a binding partner of SERT. This interaction was further verified by co-immunoprecipitation and glutathione-S-transferase pull-down assays. M6B belongs to a proteolipid protein family, which is expressed in neurons and in oligodendrocytes in the brain. The knowledge of the biological function of this protein family is sparse, but their expression in most brain regions have led to the hypothesis that they are involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. The co-expression of SERT with M6B results in a significant decrease in SERT-mediated serotonin uptake caused by a down-regulation of SERT surface expression. Furthermore, we find, using confocal microscopy, that M6B co-localizes with SERT when transiently expressed in HEK-MSR-293 cells and when endogenously expressed in RN46A cells. Taken together, our data suggest that M6B regulates the serotonin uptake by affecting cellular trafficking of the serotonin transporter.
authors.affiliation: Centre for Psychiatric Research, University Hospital of Aarhus, Risskov, Denmark.
authors.forename: Anja Winther
authors.initials: AW
authors.lastname: Fjorback
authors.forename: Heidi Kaastrup
authors.initials: HK
authors.lastname: Müller
authors.forename: Ove
authors.initials: O
authors.lastname: Wiborg
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: C484158:GPM6A protein, human; C484160:GPM6B protein, human; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin