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.

Isolation of putative stem cells present in human adult olfactory mucosa

“…In addition, a two-fold increase in Glycoprotein M6B (GPM6B) expression levels is also present in our cells. Glycoprotein M6B represents a neuroplasticity-related gene that interacts with the serotonin transporter and is down-regulated in the hippocampus of chronically stressed animals and in cases of depressed suicides [34, 35]. A further interesting example is Roundabout, Axon Guidance Receptor, Homolog 1 (ROBO1) whose expression is implicated in several tumors of the nervous system: a low expression of ROBO1 is related to brain metastasis indicating a poor prognosis, whereas a high expression is common in gliomas [36, 37].…”

Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry

“…The association was in an intron of the gene GPM6B (Neuronal Membrane Glycoprotein M6B), which is implicated in the internalization of the serotonin transporter 10 . Gpm6B-deficient mice exhibit deficient prepulse inhibition and an altered response to the 5-HT2A/C agonist DOI 11 .…”

Actin-Independent Behavior and Membrane Deformation Exhibited by the Four-Transmembrane Protein M6a

“…Among them, we can acknowledge their potential involvement in membrane dynamics. More specifically, heterologous expression analyses have shown that M6a and M6b affect membrane trafficking and cell surface expression of G protein-coupled receptors such as the μ-opioid receptor and the serotonin transporter [21], [22], [23]. As the most abundant protein in the myelin membrane, PLP/DM20 is synthesized by oligodendrocytes, regulates the regularly-spaced apposition of myelin membranes, and maintains their stability [24], [25], [26].…”