Calcium/calmodulin-dependent protein kinase II (CaMKII) has diverse roles in virtually all cell types and it is regulated by a plethora of mechanisms. Local changes in Ca2+ concentration drive calmodulin binding and CaMKII activation. Activity is controlled further by autophosphorylation at multiple sites, which can generate an autonomously active form of the kinase (Thr286) or can block Ca2+/calmodulin binding (Thr305/306). The regulated actions of protein phosphatases at these sites also modulate downstream signalling from CaMKII. In addition, CaMKII targeting to specific subcellular microdomains appears to be necessary to account for the known signalling specificity, and targeting is regulated by Ca2+/calmodulin and autophosphorylation. The present review focuses on recent studies revealing the diversity of CaMKII interactions with proteins localized to neuronal dendrites. Interactions with various subunits of the NMDA (N-methyl-d-aspartate) subtype of glutamate receptor have attracted the most attention, but binding of CaMKII to cytoskeletal and several other regulatory proteins has also been reported. Recent reports describing the molecular basis of each interaction and their potential role in the normal regulation of synaptic transmission and in pathological situations are discussed. These studies have revealed fundamental regulatory mechanisms that are probably important for controlling CaMKII functions in many cell types.
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Review Article|
February 15 2004
Targeting of calcium/calmodulin-dependent protein kinase II
Roger J. COLBRAN
Roger J. COLBRAN
1
Department of Molecular Physiology and Biophysics, The Center for Molecular Neuroscience and The Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, TN 37232, U.S.A.
1e-mail roger.colbran@vanderbilt.edu
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Publisher: Portland Press Ltd
Received:
October 09 2003
Revision Received:
December 03 2003
Accepted:
December 04 2003
Accepted Manuscript online:
December 04 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 378 (1): 1–16.
Article history
Received:
October 09 2003
Revision Received:
December 03 2003
Accepted:
December 04 2003
Accepted Manuscript online:
December 04 2003
Citation
Roger J. COLBRAN; Targeting of calcium/calmodulin-dependent protein kinase II. Biochem J 15 February 2004; 378 (1): 1–16. doi: https://doi.org/10.1042/bj20031547
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