Alternative splicing generates two variants of the alpha 1 subunit of the inhibitory glycine receptor.
The inhibitory glycine receptor (GlyR) in mammalian spinal cord displays pharmacological and molecular heterogeneity of its strychnine binding alpha subunit. Here, cDNAs were isolated which encode a variant (alpha ins 1) of the rat GlyR alpha 1 subunit that contains eight additional amino acids in its putative cytoplasmic domain. Analysis of the corresponding genomic sequence showed that alpha ins 1 transcripts result from alternative splice acceptor site selection. S1 nuclease protection experiments, Northern blot analysis, and RNA amplification by polymerase chain reaction revealed alpha 1 and alpha ins 1 mRNA in postnatal spinal cord, but not in other brain regions. Expression of synthetic alpha ins 1 RNA in Xenopus oocytes generated glycine-gated strychnine-sensitive chloride channels. These data indicate that alternative splicing contributes to GlyR alpha subunit heterogeneity in the mammalian central nervous system.
Zentrum für Molekulare Biologie, Universität Heidelberg, Federal Republic of Germany.
M L
ML
Malosio
G
G
Grenningloh
J
J
Kuhse
V
V
Schmieden
B
B
Schmitt
P
P
Prior
H
H
Betz
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D015183:Restriction Mapping; D013116:Spinal Cord / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology; D014158:Transcription, Genetic; D014981:Xenopus
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D013331:Strychnine