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Alzheimer's molecule is a smart speed bump on the nerve-cell transport highway
Date:1/17/2008

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine discovered that proteins carrying chemical cargo in nerve cells react differently when exposed to the tau protein, which plays an important role in Alzheimers disease.

Dynein and kinesin proteins transport cellular cargo towards opposite ends of tracks called microtubules. Tau binds to the microtubule surface and acts like a speed bump to regulate protein traffic, the group found. But it is a smart speed bump because it impedes these different motor proteins to different degrees, explains first author Ram Dixit, PhD, a postdoctoral fellow in the lab of senior author Erika Holzbaur, PhD, Professor of Physiology.

Our findings show a mechanism of regulating the transport of nutrients, signaling molecules, and waste proteins along a nerve cells axon, says Dixit. Neurodegenerative diseases such as Alzheimers arise when pieces of this shipping system goes awry.

The transport performed by dynein and kinesin is required for continuously providing new proteins to the axon and synapse to maintain normal cellular function, and is also required to remove old, misfolded, or aggregated proteins for degradation. Just as important, this transport is required for moving other proteins from the nerve-cell synapse back to the cell body, which is also required to maintain healthy neurons.

In neurons, microtubules are abundantly decorated with tau. Dynein and kinesin encounter the tau molecules on their travels along the microtubules. The Penn group found that dynein, which carries loads towards the interior of the cell, maneuvers around tau; whereas, kinesin, which carries loads towards the outside of the cell, detaches when it encounters tau.

These findings appear online January 17 in Science in advance of print publication.

Dynein and kinesins individual maneuverings when encountering tau allow for the cell to be able to offload cargo whe
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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