Cloning, transport properties, and differential localization of two splice variants of GLT-1 in the rat CNS: implications for CNS glutamate homeostasis.
At least two splice variants of GLT-1 are expressed by rat brain astrocytes, albeit in different membrane domains. There is at present only limited data available as to the spatial relationship of such variants relative to the location of synapses and their functional properties. We have characterized the transport properties of GLT-1v in a heterologous expression system and conclude that its transport properties are similar to those of the originally described form of GLT-1, namely GLT-1alpha. We demonstrate that GLT-1alpha is localized to glial processes, some of which are interposed between multiple synapse types, including GABAergic synapses, whereas GLT-1v is expressed by astrocytic processes, at sites not interposed between synapses. Both splice variants can be expressed by a single astrocyte, but such expression is not uniform over the surface of the astrocytes. Neither splice variant of GLT-1 is evident in brain neurons, but both are abundantly expressed in some retinal neurons. We conclude that GLT-1v may not be involved in shaping the kinetics of synaptic signaling in the brain, but may be critical in preventing spillover of glutamate between adjacent synapses, thereby regulating intersynaptic glutamatergic and GABAergic transmission. Furthermore, GLT-1v may be crucial in ensuring that low levels of glutamate are maintained at extrasynaptic locations, especially in pathological conditions such as ischemia, motor neurone disease, and epilepsy.
Sullivan
Robert
R
School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, Australia.
Rauen
Thomas
T
Fischer
Frauke
F
Wiessner
Michael
M
Grewer
Christof
C
Bicho
Ana
A
Pow
David V
DV
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001693:Biological Transport, Active / Q000502:physiology; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D012160:Retina / Q000166:cytology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018076:DNA, Complementary; D027342:Excitatory Amino Acid Transporter 2; D020033:Protein Isoforms; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid