Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons

Hai Qian, Tommaso Patriarchi, Jennifer L. Price, Lucas Matt, Boram Lee, Madeline Nieves-Cintrón, Olivia R. Buonarati, Dhrubajyoti Chowdhury, Evanthia Nanou, Matthew A. Nystoriak, William A. Catterall, Montatip Poomvanicha, Franz Hofmann, Manuel F. Navedo, Johannes W. Hell

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The L-type Ca2+ channel Cav1.2 controls multiple functions throughout the body including heart rate and neuronal excitability. It is a key mediator of fight-or-flight stress responses triggered by a signaling pathway involving b-adrenergic receptors (bARs), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). PKA readily phosphorylates Ser1928 in Cav1.2 in vitro and in vivo, including in rodents and humans. However, S1928A knock-in (KI) mice have normal PKA-mediated L-type channel regulation in the heart, indicating that Ser1928 is not required for regulation of cardiac Cav1.2 by PKA in this tissue. We report that augmentation of L-type currents by PKA in neurons was absent in S1928A KI mice. Furthermore, S1928A KI mice failed to induce long-term potentiation in response to prolonged theta-tetanus (PTT-LTP), a form of synaptic plasticity that requires Cav1.2 and enhancement of its activity by the β2-adrenergic receptor (β2AR)-cAMP-PKA cascade. Thus, there is an unexpected dichotomy in the control of Cav1.2 by PKA in cardiomyocytes and hippocampal neurons.

Original languageEnglish (US)
Article numberaaf9659
JournalScience Signaling
Volume10
Issue number463
DOIs
StatePublished - Jan 24 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Qian, H., Patriarchi, T., Price, J. L., Matt, L., Lee, B., Nieves-Cintrón, M., Buonarati, O. R., Chowdhury, D., Nanou, E., Nystoriak, M. A., Catterall, W. A., Poomvanicha, M., Hofmann, F., Navedo, M. F., & Hell, J. W. (2017). Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons. Science Signaling, 10(463), [aaf9659]. https://doi.org/10.1126/scisignal.aaf9659