Regulations of Calcineurin B Subunit and Calmodulin on Calcineurin A Subunit with Tau and Its Truncation Mutant as Substrates: Regulations of CNB and CaM on CNA with tau substrate

摘要

Calcineurin (CN) is a heterodimer of a catalytic subunit, calcineurin A (CNA), and a regulatory subunit, calcineurin B (CNB), and is unique in being regulated by Ca2+, together with calmodulin (CaM). Previously, RII peptide and pnitrophenyl phosphate were often applied as substrates to explore how CNA activity was regulated by CNB and CaM. Here, by using tau, a physiological substrate of CN, and its truncation mutant tau50 as substrates, the specific effects of CNB and CaM were compared. Activity assays and kinetic analyses revealed that alone CNB failed to regulate CNA and its truncation mutant CNAabc, and CaM not only regular CNA, but also stimulate the regulation of CNB on CNA. It was found that CNB and CaM were all not required by CNA to associate with tau, and the efficiencies of CN to dephosphorylate tau keep constant regardless of whether CNB and/or CaM are present or not. The findings may be valuable for revealing how CN take part in controlling phosphorylation of tau in vivo and the pathogenesis of tauopathies such as Alzheimer's Disease.