Glutamate transporter protein subtypes are expressed differentially during rat CNS development.
Extracellular glutamate concentrations are regulated by glial and neuronal transporter proteins. Four glutamate transporter subtypes have been identified in rat brain; GLAST and GLT-1 are primarily astrocytic, whereas EAAC1 and EAAT4 are neuronal. Using immunoblotting and immunohistochemistry with subtype-specific antipeptide antibodies, we examined the protein expression and regional and cellular localization of each glutamate transporter subtype in embryonic and postnatal rat CNS. Each transporter had a specific pattern of expression. GLAST immunoreactivity was low prenatally but became enriched in cerebellar Bergmann glia early postnatally and then was also present in forebrain later postnatally. The post-translational modification of GLAST was unique among the subtypes; glycosylated GLAST increased with maturation, whereas nonglycosylated protein decreased in abundance postnatally. GLT-1 was present in fetal brain and spinal cord, with expression progressively increasing to adult levels throughout the neuraxis by postnatal day 26. Transient expression of GLT-1 immunoreactivity along axonal pathways was observed prenatally, in contrast to the exclusive localization of GLT-1 to astrocytes in the adult CNS. EAAC1, localized to neurons, was enriched in forebrain, diencephalon, and hindbrain during prenatal and postnatal development. EAAC1 expression was greater in newborn brain compared with adult brain. EAAT4 had a region-specific distribution; EAAT4 was mainly in cerebellum, localized to Purkinje cells, with much lower levels in forebrain. EAAT4 levels increased in cerebellum with age. We conclude that during CNS development the expression of glutamate transporter subtypes is differentially regulated, regionally segregated, and coordinated.
Furuta
A
A
Department of Neurology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Rothstein
J D
JD
Martin
L J
LJ
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002531:Cerebellum / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D003342:Corpus Striatum / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D005326:Fetal Proteins / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D005917:Globus Pallidus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins; D006031:Glycosylation; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D019579:Neocortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D027981:Symporters
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D005326:Fetal Proteins; D050491:Glutamate Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017470:Receptors, Glutamate; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; C493389:Slc1a6 protein, rat; D027981:Symporters