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

Nature. 1999 Oct 21;401(6755):800-4. doi: 10.1038/44586.

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