Interactions Between Calcineurin, Tau, And Rcan1-1: A Disordered Trio

Calcineurin (CaN) is a highly-conserved, heterodimeric Ser/Thr phosphatase that plays vital roles in memory development and retention, cardiac growth, and immune system activation. Alterations in the regulation of CaN have been noted to contribute the development of Alzheimer's disease (AD). CaN is known to dephosphorylate the microtubule-binding protein tau, helping to regulate stabilization of microtubules. There is evidence that Rcan1-1, an endogenous inhibitor of CaN, is overexpressed in AD, suppressing CaN activity and potentially contributing to the hyperphoshorylation of tau that is a hallmark of the disorder. Interestingly, CaN contains an essential intrinsically disordered region, tau is known to be an intrinsically disordered protein (IDP), and Rcan1-1 appears to be an IDP. Here we present our initial studies of the interactions between CaN and tau, and how these are disrupted by Rcan1-1.