Intracellular Ca2+ stores modulate SOCCs and NMDA receptors via tyrosine kinases in rat hippocampal neurons

Research output: Contribution to journalArticle

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Abstract

The regulation of intracellular Ca(2+) signalling by phosphorylation processes remains poorly defined, particularly with regards to tyrosine phosphorylation. Evidence from non-excitable cells implicates tyrosine phosphorylation in the activation of so-called store-operated Ca(2+) channels (SOCCs), but their involvement in neuronal Ca(2+) signalling is still elusive. In the present study, we determined the role of protein tyrosine kinases (PTKs) and tyrosine phosphatases (PTPs) in the coupling between intracellular Ca(2+) stores and SOCCs in neonatal rat hippocampal neurons by Fura-2 Ca(2+) imaging. An early Ca(2+) response from intracellular stores was triggered with thapsigargin, and followed by a secondary plasma membrane Ca(2+) response. This phase was blocked by the non-specific Ca(2+) channel blocker NiCl and the SOCC blocker, 2-aminoethoxydiphenyl borate (2-APB). Interestingly, two structurally distinct PTK inhibitors, genistein and AG126, also inhibited this secondary response. Application of the PTP inhibitor sodium orthovanadate (OV) also activated a sustained and tyrosine kinase dependent Ca(2+) response, blocked by NiCl and 2-APB. In addition, OV resulted in a Ca(2+) store dependent enhancement of NMDA responses, corresponding to, and occluding the signalling pathway for group I metabotropic glutamate receptors (mGluRs). This study provides first evidence for tyrosine based phospho-regulation of SOCCs and NMDA signalling in neurons.
Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalCell Calcium
Volume46
Issue number1
DOIs
Publication statusPublished - Jul 2009

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N-Methyl-D-Aspartate Receptors
Protein-Tyrosine Kinases
Tyrosine
Neurons
Vanadates
Phosphorylation
N-Methylaspartate
Phosphoric Monoester Hydrolases
Metabotropic Glutamate Receptors
Thapsigargin
Genistein
Fura-2
Protein Kinase Inhibitors
Sodium
Cell Membrane
2-aminoethoxydiphenyl borate

Keywords

  • animals
  • boron compounds
  • calcium
  • calcium channels
  • calcium signaling
  • genistein
  • hippocampus
  • homeostasis
  • N-methylaspartate
  • neurons
  • phosphorylation
  • potassium chloride
  • protein tyrosine phosphatases
  • protein-tyrosine kinases
  • rats
  • rats, sprague-dawley
  • receptors, metabotropic glutamate
  • receptors, N-Methyl-D-Aspartate
  • thapsigargin
  • vanadates
  • phosphatases
  • kinases
  • store-operated calcium channel
  • metabotropic glutamate receptors
  • culture

Cite this

Intracellular Ca2+ stores modulate SOCCs and NMDA receptors via tyrosine kinases in rat hippocampal neurons. / Koss, David J; Riedel, Gernot; Platt, Bettina.

In: Cell Calcium, Vol. 46, No. 1, 07.2009, p. 39-48.

Research output: Contribution to journalArticle

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abstract = "The regulation of intracellular Ca(2+) signalling by phosphorylation processes remains poorly defined, particularly with regards to tyrosine phosphorylation. Evidence from non-excitable cells implicates tyrosine phosphorylation in the activation of so-called store-operated Ca(2+) channels (SOCCs), but their involvement in neuronal Ca(2+) signalling is still elusive. In the present study, we determined the role of protein tyrosine kinases (PTKs) and tyrosine phosphatases (PTPs) in the coupling between intracellular Ca(2+) stores and SOCCs in neonatal rat hippocampal neurons by Fura-2 Ca(2+) imaging. An early Ca(2+) response from intracellular stores was triggered with thapsigargin, and followed by a secondary plasma membrane Ca(2+) response. This phase was blocked by the non-specific Ca(2+) channel blocker NiCl and the SOCC blocker, 2-aminoethoxydiphenyl borate (2-APB). Interestingly, two structurally distinct PTK inhibitors, genistein and AG126, also inhibited this secondary response. Application of the PTP inhibitor sodium orthovanadate (OV) also activated a sustained and tyrosine kinase dependent Ca(2+) response, blocked by NiCl and 2-APB. In addition, OV resulted in a Ca(2+) store dependent enhancement of NMDA responses, corresponding to, and occluding the signalling pathway for group I metabotropic glutamate receptors (mGluRs). This study provides first evidence for tyrosine based phospho-regulation of SOCCs and NMDA signalling in neurons.",
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N2 - The regulation of intracellular Ca(2+) signalling by phosphorylation processes remains poorly defined, particularly with regards to tyrosine phosphorylation. Evidence from non-excitable cells implicates tyrosine phosphorylation in the activation of so-called store-operated Ca(2+) channels (SOCCs), but their involvement in neuronal Ca(2+) signalling is still elusive. In the present study, we determined the role of protein tyrosine kinases (PTKs) and tyrosine phosphatases (PTPs) in the coupling between intracellular Ca(2+) stores and SOCCs in neonatal rat hippocampal neurons by Fura-2 Ca(2+) imaging. An early Ca(2+) response from intracellular stores was triggered with thapsigargin, and followed by a secondary plasma membrane Ca(2+) response. This phase was blocked by the non-specific Ca(2+) channel blocker NiCl and the SOCC blocker, 2-aminoethoxydiphenyl borate (2-APB). Interestingly, two structurally distinct PTK inhibitors, genistein and AG126, also inhibited this secondary response. Application of the PTP inhibitor sodium orthovanadate (OV) also activated a sustained and tyrosine kinase dependent Ca(2+) response, blocked by NiCl and 2-APB. In addition, OV resulted in a Ca(2+) store dependent enhancement of NMDA responses, corresponding to, and occluding the signalling pathway for group I metabotropic glutamate receptors (mGluRs). This study provides first evidence for tyrosine based phospho-regulation of SOCCs and NMDA signalling in neurons.

AB - The regulation of intracellular Ca(2+) signalling by phosphorylation processes remains poorly defined, particularly with regards to tyrosine phosphorylation. Evidence from non-excitable cells implicates tyrosine phosphorylation in the activation of so-called store-operated Ca(2+) channels (SOCCs), but their involvement in neuronal Ca(2+) signalling is still elusive. In the present study, we determined the role of protein tyrosine kinases (PTKs) and tyrosine phosphatases (PTPs) in the coupling between intracellular Ca(2+) stores and SOCCs in neonatal rat hippocampal neurons by Fura-2 Ca(2+) imaging. An early Ca(2+) response from intracellular stores was triggered with thapsigargin, and followed by a secondary plasma membrane Ca(2+) response. This phase was blocked by the non-specific Ca(2+) channel blocker NiCl and the SOCC blocker, 2-aminoethoxydiphenyl borate (2-APB). Interestingly, two structurally distinct PTK inhibitors, genistein and AG126, also inhibited this secondary response. Application of the PTP inhibitor sodium orthovanadate (OV) also activated a sustained and tyrosine kinase dependent Ca(2+) response, blocked by NiCl and 2-APB. In addition, OV resulted in a Ca(2+) store dependent enhancement of NMDA responses, corresponding to, and occluding the signalling pathway for group I metabotropic glutamate receptors (mGluRs). This study provides first evidence for tyrosine based phospho-regulation of SOCCs and NMDA signalling in neurons.

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KW - phosphatases

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KW - metabotropic glutamate receptors

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