Tau cDNAs from each of the six human isoforms were transfected into CO
S- 1 cells and, in every case, more than one peptide was observed. The
diversity of expressed isoforms was due to different levels of tau ph
osphorylation. Tau phosphorylation results in a decrease of the protei
n electrophoretic mobility. The major contribution to this mobility sh
ift is due to the phosphorylation at the at the C-terminus of the mole
cule, as inferred from the expression of tau fragments. Phosphorylatio
n takes place in some of the sites modified in neural cells and in the
basis of AD patients. Copolymerization studies indicate that the leve
l of phosphorylation, as well as the localization of the modified resi
dues, may affect the binding of the protein to microtubules. These res
ults indicate that phosphorylation regulates tau function inside the c
ell.