Tau binds both subunits of calcineurin, and binding is impaired by calmodulin.
Calcineurin, an important protein Ser/Thr phosphatase which acts on tau in vivo, is a heterodimer of a catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, and is unique in being regulated by calmodulin. Here, we find that both subunits of calcineurin bind tau, and calmodulin interferes with the association between calcineurin and tau. The domains of both subunits of calcineurin and tau involved in binding are mapped. We also investigate the functional consequences of the interactions between both subunits of calcineurin, tau and calmodulin, and reveal the interactions affect dephosphorylation of tau by calcineurin and contribute to the balance of phosphorylation and dephosphorylation of tau in vivo. Our findings may be of potential significance in neuronal physiology and also in neurodegenerative disorders. They shed some light on how the interactions might control the phosphorylation state of tau under physiological conditions, and provide new insights into the treatment of tauopathies such as Alzheimer's disease.
Yu
Da-yu
DY
Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, China.
Tong
Li
L
Song
Gao-jie
GJ
Lin
Wei-lin
WL
Zhang
Lai-qun
LQ
Bai
Wei
W
Gong
He
H
Yin
Yan-xia
YX
Wei
Qun
Q
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D019703:Calcineurin / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology*; D002846:Chromatography, Affinity; D004258:DNA Polymerase III; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*
D002147:Calmodulin; D014157:Transcription Factors; C041273:transcription factor tau; D004258:DNA Polymerase III; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases