Vascular CaMKII: heart and brain in your arteries.
First characterized in neuronal tissues, the multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key signaling component in several mammalian biological systems. Its unique capacity to integrate various Ca(2+) signals into different specific outcomes is a precious asset to excitable and nonexcitable cells. Numerous studies have reported roles and mechanisms involving CaMKII in brain and heart tissues. However, corresponding functions in vascular cell types (endothelium and vascular smooth muscle cells) remained largely unexplored until recently. Investigation of the intracellular Ca(2+) dynamics, their impact on vascular cell function, the regulatory processes involved and more recently the spatially restricted oscillatory Ca(2+) signals and microdomains triggered significant interest towards proteins like CaMKII. Heteromultimerization of CaMKII isoforms (four isoforms and several splice variants) expands this kinase's peculiar capacity to decipher Ca(2+) signals and initiate specific signaling processes, and thus controlling cellular functions. The physiological functions that rely on CaMKII are unsurprisingly diverse, ranging from regulating contractile state and cellular proliferation to Ca(2+) homeostasis and cellular permeability. This review will focus on emerging evidence of CaMKII as an essential component of the vascular system, with a focus on the kinase isoform/splice variants and cellular system studied.
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada; Department of Molecular and Integrative Physiology, Université de Montréal, Montreal Quebec, Canada;
Fanny
F
Toussaint
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada; Department of Pharmacology, Université de Montréal, Montreal Quebec, Canada;
Chimène
C
Charbel
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal Quebec, Canada; and Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal Quebec, Canada.
Bruce G
http://orcid.org/0000-0001-9000-9495
BG
Allen
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal Quebec, Canada; and jonathan.ledoux@umontreal.ca.
Jonathan
J
Ledoux
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D020033:Protein Isoforms; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
CaMKII; calcium signaling; endothelium; vascular smooth muscle