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The Journal of Neuroscience, January 15, 2003, 23(2):550-560
Neutral Amino Acid Transporter ASCT1 Is Preferentially Expressed in L-Ser-Synthetic/Storing Glial Cells in the Mouse Brain with Transient Expression in Developing Capillaries
Kazuhisa Sakai1, 2, *, Hidemi Shimizu1, *, Tatsuro Koike2, Shigeki Furuya3, and Masahiko Watanabe1 1 Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, 2 Molecular Neurobiology Laboratory, Hokkaido University Graduate School of Science, Sapporo 060-0810, Japan, and 3 Neuronal Circuit Mechanisms Research Group, The Institute of Physical and Chemical Research (RIKEN) Brain Science Institute, Wako, Saitama 351-0198, Japan
Nonessential amino acid L-Ser plays an essential role in neuronal survival and differentiation, through preferential expression of the L-Ser biosynthetic enzyme 3-phosphoglycerate dehydrogenase (3PGDH), in particular in glial cells but not in neurons. To seek the molecular candidates responsible for glia-borne L-Ser transport, we performed histochemical analyses on amino acid transporter ASCT1, which prefers small neutral amino acids, such as Ala, Ser, Cys, and Thr, and mediates their obligatory exchange. At early developmental stages, neuroepithelial cells constituting the ventricular zone expressed ASCT1 mRNA and protein ubiquitously. Thereafter, ASCT1 expression was gradually downregulated in neuronal populations during the late embryonic and neonatal periods, whereas its high expression was transmitted to radial glial cells and then to astrocytes. High levels of ASCT1 were also detected in the olfactory ensheathing glia. The preferential glial expression of ASCT1 was consistent with that of 3PGDH, and their extensive colocalization was demonstrated at the cellular level. Moreover, high cellular contents of L-Ser were revealed in these glial cells by using a specific antibody to L-Ser. These results strongly suggest that a large amount of L-Ser is synthesized and stored in these glial cells and is released through ASCT1 in exchange for other extracellular substrates. In addition, we observed prominent expression of ASCT1 in capillary endothelial cells of embryonic and neonatal brains. Therefore, ASCT1 appears to be regulated to meet metabolic demands by differentiating and mature neurons through the transport of glia- and blood-borne small neutral amino acids.
Key words: amino acid transporter; ASCT1; L-Ser; astrocyte; capillary; brain; blood-brain barrier
* K.S. and H.S. contributed equally to this work.
Copyright © 2003 Society for Neuroscience 0270-6474/03/232550-11$05.00/0
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