alpha-calcium-calmodulin-dependent kinase II is associated with paired helical filaments of Alzheimer's disease.
Alzheimer's disease (AD) is characterized pathologically by two distinguishable deposits in the brain, namely senile plaques and neurofibrillary tangles (NFT). Senile plaques are composed of fragments of the amyloid precursor protein, whereas NFT are composed primarily of paired-helical filaments (PHF). The latter are in turn composed principally of the microtubule-associated protein, tau. Tau in PHF is highly and unusually phosphorylated but the mechanisms leading to this unusual phosphorylation are not known. Using a combination of immunoblotting and kinase assays, we demonstrate that a discreet set of kinases copurify with PHF. One of these kinases was found by immunoblotting to be alpha-calcium-calmodulin-dependent kinase II (alpha-CaM kinase). Immunogold labeling revealed that alpha-CaM kinase was localized to a novel globular membranelike structure found at the ends of PHF. Since previous studies have shown alpha-CaM kinase to be involved in memory, its association with PHF may have important implications in understanding memory loss in AD. We also discuss the possibility that the association of alpha-CaM kinase with PHF may indicate sites where tau protein is converted into PHF.
Xiao
J
J
Medical Biotechnology Center of the University of Maryland Biotechnology Institute, University of Maryland School of Medicine, Baltimore 21205, USA.
Perry
G
G
Troncoso
J
J
Monteiro
M J
MJ
D000544:Alzheimer Disease / Q000201:enzymology*; D000918:Antibody Specificity; D001923:Brain Chemistry / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D016900:Neurofilament Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology
D016900:Neurofilament Proteins; C517657:CAMK2A protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases