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Vol. 19, Issue 4, 1485-1498, April 2008

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The Microtubule-severing Proteins Spastin and Katanin Participate Differently in the Formation of Axonal Branches

Wenqian Yu^*,, Liang Qiang^*,, Joanna M. Solowska^*, Arzu Karabay^*,, Sirin Korulu^*,, and Peter W. Baas^*

*Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129; and Department of Molecular Biology and Genetics, Istanbul Technical University, 34469 Istanbul, Turkey

Submitted September 7, 2007; Revised November 21, 2007; Accepted January 18, 2008
Monitoring Editor: Erika Holzbaur

Neurons express two different microtubule-severing proteins, namely P60-katanin and spastin. Here, we performed studies on cultured neurons to ascertain whether these two proteins participate differently in axonal branch formation. P60-katanin is more highly expressed in the neuron, but spastin is more concentrated at sites of branch formation. Overexpression of spastin dramatically enhances the formation of branches, whereas overexpression of P60-katanin does not. The excess spastin results in large numbers of short microtubules, whereas the excess P60-katanin results in short microtubules intermingled with longer microtubules. We hypothesized that these different microtubule-severing patterns may be due to the presence of molecules such as tau on the microtubules that more strongly shield them from being severed by P60-katanin than by spastin. Consistent with this hypothesis, we found that axons depleted of tau show a greater propensity to branch, and that this is true whether or not the axons are also depleted of spastin. We propose that there are two modes by which microtubule severing is orchestrated during axonal branch formation, one based on the local concentration of spastin at branch sites and the other based on local detachment from microtubules of molecules such as tau that regulate the severing properties of P60-katanin.

These authors contributed equally to this work.

Address correspondence to: Peter W. Baas (pbaas{at}drexelmed.edu).

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