Modelling the Effects of Microtubule Plus End Tapering on EB1 Binding

Abstract

Fluorescence (smTIRF) Microscopy. Contrary to the canonical theory, we determined the R5L mutation does not reduce Tau affinity for the microtubule. Rather, the R5L mutation reduces the total amount of Tau bound to the microtubule at saturating conditions. Our data suggests the R5L mutation reduces Tau:Tau interactions, decreasing the ability of R5L-Tau to form larger order complexes, known as ''Tau condensates.'' Currently, we are determining the mechanism by which this occurs, potentially due to a structural change associated with the R5L mutation. Altogether, these results challenge the current paradigm of how mutations in Tau lead to disease.