Identification of a vesicular nucleotide transporter.
ATP is a major chemical transmitter in purinergic signal transmission. Before secretion, ATP is stored in secretory vesicles found in purinergic cells. Although the presence of active transport mechanisms for ATP has been postulated for a long time, the proteins responsible for its vesicular accumulation remains unknown. The transporter encoded by the human and mouse SLC17A9 gene, a novel member of an anion transporter family, was predominantly expressed in the brain and adrenal gland. The mouse and bovine counterparts were associated with adrenal chromaffin granules. Proteoliposomes containing purified transporter actively took up ATP, ADP, and GTP by using membrane potential as the driving force. The uptake properties of the reconstituted transporter were similar to that of the ATP uptake by synaptic vesicles and chromaffin granules. Suppression of endogenous SLC17A9 expression in PC12 cells decreased exocytosis of ATP. These findings strongly suggest that SLC17A9 protein is a vesicular nucleotide transporter and should lead to the elucidation of the molecular mechanism of ATP secretion in purinergic signal transmission.
Sawada
Keisuke
K
Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Echigo
Noriko
N
Juge
Narinobu
N
Miyaji
Takaaki
T
Otsuka
Masato
M
Omote
Hiroshi
H
Yamamoto
Akitsugu
A
Moriyama
Yoshinori
Y
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005089:Exocytosis; D006160:Guanosine Triphosphate; D006801:Humans; D051379:Mice; D033704:Nucleotide Transport Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000302:isolation & purification / Q000378:metabolism*
D033704:Nucleotide Transport Proteins; D009711:Nucleotides; C529437:Slc17a9 protein, human; C578984:Slc17a9 protein, mouse; D033921:Vesicular Transport Proteins; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate