Tau-isoform dependent enhancement of taxol mobility through microtubules

Abstract

Tau, a family of microtubule-associated proteins (MAPS), stabilizes microtubules (MTs) and regulates their dynamics. Tau isoforms regulate MT dynamic instability differently: 3-repeat tau is less effective than 4-repeat tau at Suppressing the disassembly of MTs. Here, we report another tau-isoforn-dependent phenomenon, revealed by fluorescence recovery after photobleaching measurements on a BODIPY-conjugated taxol bound to MTs. Saturating levels of recombinant full-length 3-repeat and 4-repeat tau both cause taxol mobility to be remarkably sensitive to taxol concentration. However, 3-repeat tau induces 2.5-fold faster recovery (similar to 450 s) at low taxol concentrations (similar to 100 nM) than 4-repeat tau (similar to 1000 s), indicating that 3-repeat tau decreases the probability of taxol rebinding to its site in the MT lumen. Finding no tau-induced change in the MT-binding affinity Of taxol, We Conclude that 3-repeat tau either competes for the taxol binding site with an affinity of similar to 1 mu M or alters the MT structure so as to facilitate the passage of taxol through Pores in the MT wall. (c) 2008 Elsevier Inc. All rights reserved.