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Microtubule Polarity in Neurons

Many cells require precise arrangement of their microtubule cytoskeleton for proper directed transport, with neurons providing the most obvious example of this.  Interestingly, in living Drosophila neurons, axons contain all plus-end out microtubules, while dendrites contain all minus-end out microtubules [1].  How this geometry is initially set up and is maintained despite the fact that microtubules are continually nucleating and growing into bifurcations is not at all clear.  Melissa Rolls’ lab at PSU found that >98% of microtubules growing into bifurcations in dendrites turned toward the cell body, indicating that there must be some mechanism to properly steer the growing microtubules at junctions [2].  Through RNAi knockdowns, crosses between mutant flies, and visualization of microtubule dynamics, a working model for microtubule steering was developed.  The model holds that EB1 proteins that track the growing end of microtubules bind to Kinesin-2 motors through a bridging protein (APC), and at microtubule junctions, the motors serve to bend the tip of the growing microtubule and bias it towards the cell body, thus maintaining uniform minus-end out orientation.  We are using in vitro reconstitution experiments, computational modeling, and microfluidic channels to study the molecular details of microtubule polarity maintenance in dendrites.

Neural MT

Microtubule steering in dendrites. Growing microtubules (red) are guided along stable microtubules (blue) to turn towards the cell body, resulting in uniformly minus-end out microtubules in dendrites.  At right is model for microtubule bending through concerted actions of EB1, which binds to the plus-end of growing microtubules, and Kinesin-2.  This model is being tested using in vitro reconstitution experiments.

References:

1. Stone, M.C., Roegiers, F., and Rolls, M.M. (2008). Microtubules have opposite orientation in axons and dendrites of Drosophila neurons. Mol Biol Cell 19, 4122-4129.
2. Mattie, F.J., Stackpole, M.M., Stone, M.C., Clippard, J.R., Rudnick, D.A., Qiu, Y., Tao, J., Allender, D.L., Parmar, M., and Rolls, M.M. (2010). Directed microtubule growth, +TIPs, and kinesin-2 are required for uniform microtubule polarity in dendrites. Current Biology 20, 2169-2177.

 

Other Research Topics:

Kinesin Mechanochemistry
Chemomechanical Modeling
Nanobiotechnology and Microscale Transport
Artificial Mitotic Spindle
Microtubule Polarity in Neurons
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