Site-specific splice variation of the human P2X4 receptor.
P2X4 receptors are expressed in specific brain areas. We now describe site-specific splice variations of the human P2X4 receptor subunit, occurring at residue [YVIG / WVFV(W)] near the end of the first predicted transmembrane domain. p2X4(b) is formed by the insertion of an additional 16 amino acids. p2X4(C) is formed by deleting a cassette of 130 amino acids, including six of the 10 conserved extracellular cysteine residues. Transfection of P2X4(a), but not p2x4(c), formed functional channels in Xenopus oocytes and human 1321N1 cells. After transfection of p2X4(b) small, inconsistent ATP-evoked responses were detected only in the human cells, but when co-expressed, p2x4(b) may alter the function of P2X4(a) in oocytes. The distribution of splice variant RNA within human brain suggests regionally-dependent expression. These data indicate that the functions of the human P2X4 receptor may be altered by alternative splicing.
Carpenter
D
D
Department of Information Management, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
Meadows
H J
HJ
Brough
S
S
Chapman
G
G
Clarke
C
C
Coldwell
M
M
Davis
R
R
Harrison
D
D
Meakin
J
J
McHale
M
M
Rice
S Q
SQ
Tomlinson
W J
WJ
Wood
M
M
Sanger
G J
GJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D058848:Receptors, Purinergic P2X4; D014162:Transfection / Q000235:genetics; D014981:Xenopus
D009479:Neuropeptides; C548226:P2RX4 protein, human; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D000255:Adenosine Triphosphate; D004247:DNA