Tau Protein Forms Ion Channels

Abstract

Tau is a microtubule associated protein that is intrinsically disordered and accumulates in amyloid fibril deposits alone and in combination with other amyloid forming proteins. We have found that Tau 441 can form ion- permeable channels in planar lipid bilayers under conditions of acidic pH. The channels are irreversibly associated with the membrane and exhibit heterodisperse conductances. Acidic phospholipids enhanced channel activity. The channels are only weakly selective for cations. Zn++ does not block the channels. These channels show significant, but incomplete, similarity to the amyloid channels formed by the Alzheimer peptide Abeta, the diabetes associated peptide IAPP, the prion related PrP106-126 ,and other amyloid channel peptides. Channel forming activity may play a pathogenic role in Tau associated diseases such as Lewy Body Dementia, by causing ion leakage in target cell membranes.