Dynein and Kinesin Intersecting Tau Interfaces on Microtubules

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Dynein and Kinesin Intersecting Tau Interfaces on
Microtubules Dawn A. Bonnell, University of
Pennsylvania, DMR 0425780
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.
Model of the role of tau in the regulation of
axonal transport (below). 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.
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.
In Press Science 2008 NSEC NSF DMR 0425780