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

re it needs to go with fine-tune accuracy. Tau may determine where kinesin offloads cargo along the microtubule tracks that radiate out to the cell surface from the center, says Holzbaur. And dyneins ability to back up and go around when it encounters an obstacle such as tau may be a mechanism to ensure that it gets to the center of the cell with its important cargo.

The group conducted studies using single molecules moving along a tau-decorated microtubule to determine the effects of tau on dynein and kinesins movement. Mutations in molecular motors such as dynein and kinesin can lead to degeneration of neurons. These mutations, for example, decrease the efficiency of dynein and kinesin. This problem can lead to the accumulation of misfolded proteins in the cell, which, in turn may lead to the degeneration of the neuron.

Theres a growing theme that defects in transport are tightly associated with neurodegeneration, says Holzbaur. Its already been shown in Alzheimers disease that there is a change in the distribution of tau along microtubules. Instead of kinesin getting its cargo closer to the cells outer surface, tau accumulates in the cell body and kinesins cargo of newly synthesized proteins gets dropped early, not at the cell surface, thus causing problems. Our findings explain how that can happen.


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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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