Calmodulin binding proteins provide domains of local Ca 2+ signaling in cardiac myocytes

Jeffrey J. Saucerman, Donald M Bers

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Calmodulin (CaM) acts as a common Ca 2+ sensor for many signaling pathways, transducing local Ca 2+ signals into specific cellular outcomes. Many of CaM's signaling functions can be explained by its unique biochemical properties, including high and low affinity Ca 2+-binding sites with slow and fast kinetics, respectively. CaM is expected to have a limited spatial range of action, emphasizing its role in local Ca 2+ signaling. Interactions with target proteins further fine-tune CaM signal transduction. Here, we focus on only three specific cellular targets for CaM signaling in cardiac myocytes: the L-type Ca 2+ channel, the ryanodine receptor, and the IP 3 receptor. We elaborate a working hypothesis that each channel is regulated by two distinct functional populations of CaM: dedicated CaM and promiscuous CaM. Dedicated CaM is typically tethered to each channel and directly regulates channel activity. In addition, a local pool of promiscuous CaM appears poised to sense local Ca 2+ signals and trigger downstream pathways such as Ca 2+/CaM dependent-protein kinase II and calcineurin. Understanding how promiscuous CaM coordinates multiple distinct signaling pathways remains a challenge, but is aided by the use of mathematical modeling and a new generation of fluorescent biosensors. This article is part of a special issue entitled "Local Signaling in Myocytes.".

Original languageEnglish (US)
Pages (from-to)312-316
Number of pages5
JournalJournal of Molecular and Cellular Cardiology
Volume52
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Calmodulin-Binding Proteins
Calmodulin
Cardiac Myocytes
Protein Domains
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Ryanodine Receptor Calcium Release Channel
Calcineurin
Biosensing Techniques
Muscle Cells
Signal Transduction
Binding Sites

Keywords

  • Ca signaling
  • Calmodulin
  • Cardiac myocytes
  • Compartmentation
  • Ion channels

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Calmodulin binding proteins provide domains of local Ca 2+ signaling in cardiac myocytes. / Saucerman, Jeffrey J.; Bers, Donald M.

In: Journal of Molecular and Cellular Cardiology, Vol. 52, No. 2, 02.2012, p. 312-316.

Research output: Contribution to journalArticle

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