PT  - JOURNAL ARTICLE
AU  - Noriaki Shimokawa
AU  - Junichi Okada
AU  - Kaisa Haglund
AU  - Ivan Dikic
AU  - Noriyuki Koibuchi
AU  - Mitsuhiko Miura
TI  - Past-A, a Novel Proton-Associated Sugar Transporter, Regulates Glucose Homeostasis in the Brain
AID  - 10.1523/JNEUROSCI.22-21-09160.2002
DP  - 2002 Nov 01
TA  - The Journal of Neuroscience
PG  - 9160--9165
VI  - 22
IP  - 21
4099  - http://www.jneurosci.org/content/22/21/9160.short
4100  - http://www.jneurosci.org/content/22/21/9160.full
SO  - J. Neurosci.2002 Nov 01; 22
AB  - The ventral medullary surface (VMS) of the medulla oblongata is known to be the site of the central chemosensitive neurons in mammals. These neurons sense excess H+/CO2 dissolved in the CSF and induce hyperventilation. To elucidate the mechanism of neuronal cell adaptation to changes of H+/CO2, we screened for hypercapnia-induced genes in the VMS. Here, we report cloning and characterization of a novel gene called proton-associated sugar transporter-A (Past-A), which is induced in the brain after hypercapnia and mediates glucose uptake along the pH gradient. Past-A comprises 751 amino acid residues containing 12 membrane-spanning helices, several conserved sugar transport motifs, three proline-rich regions, and leucine repeats. Past-Atranscript was expressed predominantly in the brain. Moreover, the Past-A-immunoreactive neural cells were found in the VMS of the medulla oblongata, and the number of immunoreactive cells was increased by hypercapnic stimulation. Transient transfection of Past-A in COS-7 cells leads to the expression of a membrane-associated 82 kDa protein that possesses a glucose transport activity. The acidification of extracellular medium facilitated glucose uptake, whereas the addition of carbonyl cyanide m-chlorophenylhydrazone, a protonophore, inhibited glucose import. Together, our results indicate that Past-A is a brain-specific glucose transporter that may represent an adaptation mechanism regulating sugar homeostasis in neuronal cells after hypercapnia.