Ca2+ and pH modulate alternative splicing of exon 5 in NMDA receptor subunit 1.
RT-PCR and intracellular Ca2+ measurements were used to identify factors that modulate alternative splicing of exon 5 in the NMDA receptor transcript encoding NR1, in cultured cerebellar granule neurons. Although cells grown in media containing 5 mM KCl demonstrate compromised survival, they show the predicted developmental transition from NR1a (-exon 5) to NR1b (+exon 5) mRNA expression. This transition was blocked under culture conditions that promote survival; inclusion or exclusion of exon 5 is a reversible process that is sensitive to alterations in Ca2+ and pH. We conclude that alternative splicing of NR1 pre-mRNA transcripts may be regulated by developmental cues that modulate the degree of glutamate receptor activation.
Vallano
M L
ML
Department of Pharmacology, SUNY/Health Science Center, Syracuse, NY 13210, USA.
Beaman-Hall
C M
CM
Benmansour
S
S
D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development; D005091:Exons / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics*
D011073:Polyamines; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D011189:Potassium Chloride; D002118:Calcium