P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-1A

• Published in: Nature (London) Vol. 401; no. 6755; pp. 800 - 804
• Main Authors: Snutch, Terrance P, Sutton, Kathy G, McRory, John E, Guthrie, Heather, Murphy, Timothy H
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 21.10.1999
• Subjects: Animals; Antigens, Surface - genetics; Calcium; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium Channels, P-Type - genetics; Calcium Channels, P-Type - metabolism; Calcium Channels, Q-Type - genetics; Calcium Channels, Q-Type - metabolism; Cell Line; Cerebellum - cytology; Cerebellum - metabolism; Cyclic AMP Response Element-Binding Protein - metabolism; Feedback; Gene Expression Regulation; Humans; Ionomycin - pharmacology; Ionophores - pharmacology; Membrane Potentials; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Neurons; Neurons - metabolism; Neurotransmitters; omega-Agatoxin IVA - pharmacology; Proteins; Rats; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Synaptic Transmission; Syntaxin 1; Transfection
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/44586

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.