title: Calmodulin binding proteins provide domains of local Ca2+ signaling in cardiac myocytes.
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."
authors.affiliation: Department of Biomedical Engineering, Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA. jsaucerman@virginia.edu
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Saucerman
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism
chemical_list: D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D007473:Ion Channels; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium