RT Journal Article
SR Electronic
T1 Past-A, a Novel Proton-Associated Sugar Transporter, Regulates Glucose Homeostasis in the Brain
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9160
OP 9165
DO 10.1523/JNEUROSCI.22-21-09160.2002
VO 22
IS 21
A1 Noriaki Shimokawa
A1 Junichi Okada
A1 Kaisa Haglund
A1 Ivan Dikic
A1 Noriyuki Koibuchi
A1 Mitsuhiko Miura
YR 2002
UL http://www.jneurosci.org/content/22/21/9160.abstract
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.