Dynein and Kinesin Intersecting Tau Interfaces on Microtubules
Ram Dixit, Jennifer L. Ross, Yale E. Goldman, Erika L. F. Holzbau
Direct observation of encounters between single molecules of kinesin or dynein-dynactin (green above) and Alexa-labeled tau (red patches). The kymographs (left) show dissociation of two kinesin molecules (A) or directional reversal of two dynein-dynactin molecules (B) upon encountering a tau cluster (dotted lines). (Right) Selected images from each experiment.
Model of the role of tau in the regulation of axonal transport (right). In a healthy neuron, tau is distributed in a proximal-distal gradient (gray) that allows kinesin-driven anterograde transport from the cell body (green arrow). At the synapse, a relatively high tau concentration facilitates kinesin dissociation (red arrow). Dynein is able to bind to distal microtubules because it is less sensitive to tau. In a degenerating neuron, tau accumulates at the soma and consequently inhibits kinesin-driven anterograde transport (red blocked arrow), leading to neuro-degeneration.
Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. We conducted single-molecule studies of motor proteins moving along tau-decorated microtubules. Surprisingly, dynein tended to reverse direction, whereas kinesin tended to detach at patches of bound tau.
In Press Science 2008