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J. Biol. Chem., Vol. 276, Issue 46, 43400-43406, November 16, 2001
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From the Department of Biochemistry, Faculty of Pharmaceutical
Sciences, Okayama University, Okayama 700-8530, the ¶ Department
of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma
University, Maebashi 371-8512, and the Vesicular glutamate transporter is present in
neuronal synaptic vesicles and endocrine synaptic-like microvesicles
and is responsible for vesicular storage of
L-glutamate. A brain-specific Na+-dependent inorganic phosphate transporter
(BNPI) functions as a vesicular glutamate transporter in synaptic
vesicles, and the expression of this BNPI defines the glutamatergic
phenotype in the central nervous system (Bellocchio, E. E.,
Reimer, R. J., Fremeau, R. T., Jr., and Edwards, R. H. (2000) Science 289, 957-960; Takamori, S., Rhee, J. S., Rosenmund, C., and Jahn, R. (2000) Nature 407, 189-194). However, since not all glutamatergic neurons contain BNPI,
an additional transporter(s) responsible for vesicular glutamate uptake
has been postulated. Here we report that differentiation-associated Na+-dependent inorganic phosphate cotransporter
(DNPI), an isoform of BNPI (Aihara, Y., Mashima, H., Onda, H., Hisano,
S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue,
I., Kojima, I., and Takeda, J. (2000) J. Neurochem.
74, 2622-2625), also transports L-glutamate at the expense
of an electrochemical gradient of protons established by the vacuolar
proton pump when expressed in COS7 cells. Molecular, biological, and
immunohistochemical studies have indicated that besides its presence in
neuronal cells DNPI is preferentially expressed in mammalian
pinealocytes,
Differentiation-associated
Na+-dependent Inorganic Phosphate Cotransporter
(DNPI) Is a Vesicular Glutamate Transporter in Endocrine Glutamatergic
Systems*
§,
,
, and
Department of Physiology,
Kansai Medical University, Moriguchi, Osaka 570-8506, Japan
TC6 cells, clonal pancreatic
cells, and
cells
of Langerhans islets, these cells being proven to secrete
L-glutamate through Ca2+-dependent
regulated exocytosis followed by its vesicular storage. Pancreatic
polypeptide-secreting F cells of Langerhans islets also expressed DNPI.
These results constitute evidence that DNPI functions as another
vesicular transporter in glutamatergic endocrine cells as well as in neurons.
*
This study was supported in part by grants-in-aid for
scientific research from the Ministry of Education, Science, Sports and
Culture of Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation; the Salt Science Foundation; and the Mishima Kaiun Memorial Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Both authors contributed equally to this work.
§
Supported by a research fellowship from the Japan Society for
Promotion of Science for Young Scientists.
**
To whom correspondence should be addressed. Tel. and Fax:
81-86-251-7933; E-mail: moriyama@pheasant.pharm.okayama-u.ac.jp.
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