title: Regulation of the intracellular distribution, cell surface expression, and protein levels of AMPA receptor GluR2 subunits by the monocarboxylate transporter MCT2 in neuronal cells.
abstract: The neuronal monocarboxylate transporter, MCT2, is not only an energy substrate carrier but it is also purported to be a binding partner for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit. To unravel a putative role of MCT2 in the regulation of GluR2 subcellular distribution, Neuro2A cells and primary cultures of mouse cortical neurons were co-transfected with plasmids containing sequences to express the fluorescent proteins mStrawberry (mStb)-fused MCT2 and Venus-fused GluR2. Subsequently, their subcellular distribution was visualized by fluorescence microscopy. GluR2 was led to form perinuclear and dendritic clusters together with MCT2 when co-transfected in Neuro2A cells or in neurons, following the original distribution of MCT2. MCT2 co-transfection had no effect on the intracellular distribution of several other post-synaptic proteins, although it partially affected the intracellular distribution of GluR1 similarly to GluR2. Both cell surface and total protein expression levels of GluR2 were significantly reduced by co-expression with MCT2. Finally, partial perinuclear and dendritic co-localization between MCT2 and Rab8, a member of the small GTPase family involved in membrane trafficking of AMPA receptors, was also observed in co-transfected neurons. These results suggest that MCT2 could influence AMPA receptor trafficking within neurons by modulating GluR2 sorting between different subcellular compartments.
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Maekawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
authors.forename: Luc
authors.initials: L
authors.lastname: Pellerin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003188:Composite Resins / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics; D027501:Monocarboxylic Acid Transporters / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D003188:Composite Resins; D008164:Luminescent Proteins; D027501:Monocarboxylic Acid Transporters; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; C490426:Slc16a7 protein, mouse; C488393:Venus (composite resin); D033921:Vesicular Transport Proteins; C104722:glutamate receptor ionotropic, AMPA 2