This paper describes the physical and chemical properties of purified tau, a protein which is associated with brain microtubules and which induces assembly of microtubules from tubulin. Purified tau is composed of four polypeptides which migrate at positions equivalent to molecular weights between 55,000 and 62,000 during electrophoresis on sodium dodecyl sulfate/polyacrylamide gels. These polypeptides are shown to be closely related by peptide mapping and by amnio acid analysis. A comparison by various techniques of the high molecular weight microtubule-associated proteins with the tau polypeptides indicates no apparent relationship. Tau is found by analytical ultracentrifugation and by sedimentation equilibrium to have a sedimentation coefficient of 2.6 S and a native molecular weight of 57,000. Tau, therefore, must be highly asymmetric (an axial ratio of 20:1 using a prolate ellipsoid model), and yet possess little α-helical structure as indicated by circular dichroism. Isoelectric focusing shows tau to be a neutral or slightly basic protein. Tau is also seen to be phosphorylated by a protein kinase which copurifies with microtubules.

In the assembly process, tau apparently regulates the formation of longitudinal oligomers from tubulin dimers, and hence promotes ring formation under depolymerizing conditions and microtubule formation under polymerizing conditions. The known asymmetry of the tau molecule suggests that tau induces assembly by binding to several tubulin molecules per tau molecule, thereby effectively increasing the local concentration of tubulin and inducing the formation of longitudinal filaments. The role of tau is discussed in light of reports of polymerization induced by particular non-physiological conditions and by various polycations. The formation of normal microtubules over a wide range of tubulin and tau concentrations under mild buffer conditions suggests that tau and tubulin define a complete in vitro assembly system under conditions which approach physiological.