P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-1A.
Spatial and temporal changes in intracellular calcium concentrations are critical for controlling gene expression in neurons. In many neurons, activity-dependent calcium influx through L-type channels stimulates transcription that depends on the transcription factor CREB by activating a calmodulin-dependent pathway. Here we show that selective influx of calcium through P/Q-type channels is responsible for activating expression of syntaxin-1A, a presynaptic protein that mediates vesicle docking, fusion and neurotransmitter release. The initial P/Q-type calcium signal is amplified by release of calcium from intracellular stores and acts through phosphorylation that is dependent on the calmodulin-dependent kinase CaM K II/IV, protein kinase A and mitogen-activated protein kinase kinase. Initiation of syntaxin-1A expression is rapid and short-lived, with syntaxin-1A ultimately interacting with the P/Q-type calcium channel to decrease channel availability. Our results define an activity-dependent feedback pathway that may regulate synaptic efficacy and function in the nervous system.
Sutton
K G
KG
Biotechnology Laboratory, Dept Psychiatry University of British Columbia, Vancouver, Canada.
McRory
J E
JE
Guthrie
H
H
Murphy
T H
TH
Snutch
T P
TP
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020865:Calcium Channels, P-Type / Q000235:genetics / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005246:Feedback; D005786:Gene Expression Regulation; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D009435:Synaptic Transmission; D050827:Syntaxin 1; D014162:Transfection; D020867:omega-Agatoxin IVA / Q000494:pharmacology
D000954:Antigens, Surface; D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D017362:Cyclic AMP Response Element-Binding Protein; D007476:Ionophores; D009419:Nerve Tissue Proteins; C494212:STX1A protein, human; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D020867:omega-Agatoxin IVA; D015759:Ionomycin; D002118:Calcium