Cellular distribution of the neutral amino acid transporter subtype ASCT2 in mouse brain.
ASCT2 is an ASC (alanine-, serine-, cysteine-preferring) neutral amino acid exchanger that may regulate CNS function by transporting amino acid substrates including L-serine, L-cysteine, L-glutamine, L-glutamate and D-serine. Despite the potentially important role of ASCT2 in influencing metabolic and signaling functions of these amino acids in brain, there has been little description of its distribution in brain tissue. We employed a commercially available human ASCT2 antibody in immunohistochemistry studies in adult mouse brain and found a wide regional distribution for ASCT2 that was limited to dendrites labeled by anti-microtubule-associated protein-2 in cortex, hippocampus and striatum. No ASCT2 immunoreactivity was observed in areas labeled by antibodies against a neuronal cell body marker (NeuN), or either of the astrocyte markers, glial fibrillary acidic protein or S100beta. In cerebellum both Purkinje cell bodies and dendrites were positive for ASCT2 immunoreactivity. In support of a dendritic localization for ASCT2 in cortex, low affinity (K(T) > 1 mM), Na(+)-dependent D-serine and L-glutamine uptake characteristic of ASCT2-mediated transport was observed in P2 synaptosomal preparations. These results suggest that ASCT2 may be an important neuronal neutral amino acid transporter and highlight a discrepancy between findings of astrocyte ASCT2 function in tissue culture and brain in situ.
Gliddon
Catherine M
CM
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
Shao
Zongjun
Z
LeMaistre
Jillian L
JL
Anderson
Christopher M
CM
D026962:Amino Acid Transport System ASC / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D026962:Amino Acid Transport System ASC; D000596:Amino Acids; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C079240:Mtap2 protein, mouse; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C498850:Slc1a5 protein, mouse; D010751:Phosphopyruvate Hydratase