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Linking supply to demand: the neuronal monocarboxylate transporter MCT2 and the α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionic acid receptor GluR2/3 subunit are associated in a common trafficking process
Author(s) -
Pierre Karin,
Chatton JeanYves,
Parent Annabelle,
Repond Cendrine,
Gardoni Fabrizio,
Di Luca Monica,
Pellerin Luc
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06756.x
Subject(s) - ampa receptor , microbiology and biotechnology , glutamate receptor , dendritic spine , monocarboxylate transporter , receptor , immunolabeling , biology , transport protein , chemistry , biochemistry , transporter , neuroscience , hippocampal formation , immunohistochemistry , gene , immunology
MCT2 is the major neuronal monocarboxylate transporter (MCT) that allows the supply of alternative energy substrates such as lactate to neurons. Recent evidence obtained by electron microscopy has demonstrated that MCT2, like α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionic acid (AMPA) receptors, is localized in dendritic spines of glutamatergic synapses. Using immunofluorescence, we show in this study that MCT2 colocalizes extensively with GluR2/3 subunits of AMPA receptors in neurons from various mouse brain regions as well as in cultured neurons. It also colocalizes with GluR2/3‐interacting proteins, such as C‐kinase‐interacting protein 1, glutamate receptor‐interacting protein 1 and clathrin adaptor protein. Coimmunoprecipitation of MCT2 with GluR2/3 and C‐kinase‐interacting protein 1 suggests their close interaction within spines. Parallel changes in the localization of both MCT2 and GluR2/3 subunits at and beneath the plasma membrane upon various stimulation paradigms were unraveled using an original immunocytochemical and transfection approach combined with three‐dimensional image reconstruction. Cell culture incubation with AMPA or insulin triggered a marked intracellular accumulation of both MCT2 and GluR2/3, whereas both tumor necrosis factor α and glycine (with glutamate) increased their cell surface immunolabeling. Similar results were obtained using Western blots performed on membrane or cytoplasm‐enriched cell fractions. Finally, an enhanced lactate flux into neurons was demonstrated after MCT2 translocation on the cell surface. These observations provide unequivocal evidence that MCT2 is linked to AMPA receptor GluR2/3 subunits and undergoes a similar translocation process in neurons upon activation. MCT2 emerges as a novel component of the synaptic machinery putatively linking neuroenergetics to synaptic transmission.