Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles

We have performed a real time analysis of fluorescence-tagged vesicle and m itochondria movement in living CHO cells transfected with microtubule-assoc iated protein tau or its microtubule-binding domain. Tau does not alter the speed of moving vesicles, but it affects the frequencies of attachment and detachment to the microtubule tracks. Thus, tau decreases the run lengths both for plus-end and minus-end directed motion to an equal extent. Reversa ls from minus-end to plus-end directed movement of single vesicles are stro ngly reduced by tau, but reversals in the opposite direction (plus to minus ) are not. Analogous effects are observed with the transport of mitochondri a and even with that of vimentin intermediate filaments. The net effect is a directional bias in the minus-end direction of microtubules which leads t o the retraction of mitochondria or vimentin IFs towards the cell center. T he data suggest that tau can control intracellular trafficking by affecting the attachment and detachment cycle of the motors, in particular by reduci ng the attachment of kinesin to microtubules, whereas the movement itself i s unaffected.