Excitatory Amino Acids and the Cerebral Cortex

Abstract

gradient as its drivingforce, was unexpectedly found to be pre-dominantly localized in synaptic vesicles inspecific glutamatergic terminals of mamma-lian brain. It was reported to be localizedin intracellular vesicles when the gene wasstably transfected into Madin–Darby caninekidney (MDCK) cells. Glycosylation at thelarge extracellular loop is also importantfor targetting the transporter to theplasma membrane as well as for maintain-ing the stability of the transporter. GLYT1mutant which lacks four putative Asp gly-cosylation sites is characterized by abnor-mal targetting to the plasma membrane.Post-translational or acute modulationof transporter activity by protein phos-phorylation is one of the hottest issues inthis field today. Various agents whichstimulate or inhibit protein kinases andprotein phosphatases are reported tomodulate transport activity, and putativephosphorylation sites have been identifiedin cytoplasmic domains of each trans-porter protein. However, the effect ofdirect phosphorylation of transporter pro-tein has not been definitely demonstrated.The glutamate transporter subtype GLT1has been shown to be phosphorylated byPKC at Ser113, resulting in an increase inV