Fine tuning of glutamate uptake and degradation in glial cells: common transcriptional regulation of GLAST1 and GS.
Glutamate is the major excitatory neurotransmitter in the mammalian brain and retina, and glutamate uptake is essential for the normal function of glutamatergic synapses in the retina. As summarized here, all neuronal and macroglial cells of the retina express high-affinity glutamate transporters. GLAST1 is expressed in glial cells, whereas GLT1 and EAAC1 are neuronal. Glutamate uptake studies in intact retina revealed that Müller glial cells dominate the total retinal glutamate transport and that this uptake is strongly influenced by the activity of glutamine synthetase. A prerequisite for an effective glutamate-glutamine cycle in glial cells would be the regulated coordination between glutamate uptake and glutamate degradation. Using cultured retinal Müller glial cells, we demonstrate that protein expression of both, GLAST1 and glutamine synthetase, are inducible by the glucocorticoid hormone cortisol. These results suggest a common transcriptional regulation of the key proteins in the glial portion of the glutamate-glutamine cycle and may impact on transmitter clearance, transmitter recycling and, as discussed, on the development of the cellular architecture in retina.
Rauen
T
T
Max-Planck-Institute for Brain Research, Frankfurt, Germany. rauen@mpih-frankfurt.mpg.de
Wiessner
M
M
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D027322:Amino Acid Transport System X-AG; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000201:enzymology; D002352:Carrier Proteins / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D050491:Glutamate Plasma Membrane Transport Proteins; D005970:Glutamate Synthase / Q000096:biosynthesis* / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009457:Neuroglia / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; D027981:Symporters; D018698:Glutamic Acid; D005970:Glutamate Synthase