Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor.
We have identified a splice variant encoding only the extracellular ligand-binding domain of the gamma-aminobutyric acid B (GABA(B)) receptor subunit GABA(B(1a)). This isoform, which we have named GABA(B(1e)), is detected in both rats and humans. While GABA(B(1e)) is a minor component of the total pool of GABA(B(1)) transcripts detected in the central nervous system, it is the primary isoform found in all peripheral tissues examined. When expressed in a heterologous system, the truncated receptor is both secreted and membrane associated. However, GABA(B(1e)) lacks the ability to bind the radiolabeled antagonist [(3)H]CGP 54626A, activate G-protein coupled inwardly rectifying potassium channels, or inhibit forskolin-induced cAMP production when it is expressed alone or together with GABA(B(2)). Interestingly, when co-expressed with GABA(B(2)), not only does the truncated receptor heterodimerize with GABA(B(2)), the association is of sufficient avidity to disrupt the normal GABA(B(1a))/GABA(B(2)) association. Despite this strong interaction, GABA(B(1e)) fails to disrupt G-protein coupled inwardly rectifying potassium activation by the full-length heterodimer pair of GABA(B(1a))/GABA(B(2)).
Schwarz
D A
DA
Neurocrine Biosciences, Inc., San Diego, California 92121-1102, USA. dschwarz@neurocrine.com
Barry
G
G
Eliasof
S D
SD
Petroski
R E
RE
Conlon
P J
PJ
Maki
R A
RA
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D019281:Dimerization; D018756:GABA Antagonists / Q000378:metabolism / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009865:Oocytes; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D018080:Receptors, GABA-B / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D014162:Transfection; D014982:Xenopus laevis
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D011994:Recombinant Proteins; C107353:CGP 54626; D005576:Colforsin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins