Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, Surface / genetics*
-
Calcium / metabolism*
-
Calcium Channel Blockers / pharmacology
-
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 / metabolism
-
Rats
-
Reverse Transcriptase Polymerase Chain Reaction
-
Signal Transduction
-
Synaptic Transmission
-
Syntaxin 1
-
Transfection
-
omega-Agatoxin IVA / pharmacology
Substances
-
Antigens, Surface
-
Calcium Channel Blockers
-
Calcium Channels, P-Type
-
Calcium Channels, Q-Type
-
Cyclic AMP Response Element-Binding Protein
-
Ionophores
-
Nerve Tissue Proteins
-
STX1A protein, human
-
Stx1a protein, rat
-
Syntaxin 1
-
omega-Agatoxin IVA
-
Ionomycin
-
Calcium
Associated data
-
GENBANK/AF060538
-
GENBANK/L19760
-
GENBANK/M55047
-
GENBANK/M64373
-
GENBANK/M95734
-
GENBANK/V01227
-
GENBANK/X06389