Cytoskeleton-related trafficking of the EAAC1 glutamate transporter after activation of the G(q/11)-coupled neurotensin receptor NTS1.
The possible modulation of the glutamate transporter EAAC1 by a class A G protein-coupled receptor was studied in transfected C6 glioma cells stably expressing the high-affinity neurotensin receptor NTS1. Brief exposure (5 min) to neurotensin increased Na(+)-dependent D-[(3)H]aspartate uptake by about 70%. The effect of neurotensin was found to result from an increase in cell surface expression of EAAC1 and accordingly, cytochalasin D and colchicine were shown to block the effect of neurotensin on aspartate uptake, suggesting that the cytoskeleton participates in this regulation. Neither protein kinase C nor phosphatidylinositol 3-kinase activities, two intracellular signaling pathways known to modulate EAAC1, was required for EAAC1-mediated aspartate transport regulation by neurotensin. Together, these results provide evidence for an acute regulation of EAAC1 trafficking after activation of a G protein-coupled receptor.
Laboratoire de Pharmacologie Expérimentale, Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium. mustapha.najimi@farl.ucl.ac.be
Mustapha
M
Najimi
Jean Marie
JM
Maloteaux
Emmanuel
E
Hermans
D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D050491:Glutamate Plasma Membrane Transport Proteins; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D027981:Symporters; D014407:Tumor Cells, Cultured
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D011956:Receptors, Cell Surface; D018028:Receptors, Neurotensin; C493398:Slc1a1 protein, rat; D027981:Symporters; D001224:Aspartic Acid; D009496:Neurotensin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins