Tau Protects Microtubules in the Axon from Severing by Katanin

Drexel University, Filadelfia, Pennsylvania, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 04/2006; 26(12):3120-9. DOI: 10.1523/JNEUROSCI.5392-05.2006
Source: PubMed


Microtubules in the axon are more resistant to severing by katanin than microtubules elsewhere in the neuron. We have hypothesized that this is because of the presence of tau on axonal microtubules. When katanin is overexpressed in fibroblasts, the microtubules are severed into short pieces, but this phenomenon is suppressed by the coexpression of tau. Protection against severing is also afforded by microtubule-associated protein 2 (MAP2), which has a tau-like microtubule-binding domain, but not by MAP1b, which has a different microtubule-binding domain. The microtubule-binding domain of tau is required for the protection, but within itself, provides less protection than the entire molecule. When tau (but not MAP2 or MAP1b) is experimentally depleted from neurons, the microtubules in the axon lose their characteristic resistance to katanin. These results, which validate our hypothesis, also suggest a potential explanation for why axonal microtubules deteriorate in neuropathies involving the dissociation of tau from the microtubules.

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    • "In addition, Shot binds along MT shafts and stabilises them independent of its linkage to F-actin (Sánchez-Soriano et al., 2009; Alves-Silva et al., 2012). Other MT shaft binders are Tau which protects MTs against the MT-severing protein Katanin in axons (not shown; Qiang et al., 2006), and mammalian MAP1B can cross-link MTs as well as mediate actin-MT linkage during axon growth (Bouquet et al., 2007; Riederer, 2007). Tau, MAP1B and Shot (in an EB1-independent mode) influence MT polymerisation kinetics through yet unknown mechanisms (stippled grey arrow; Alves-Silva et al., 2012; Feinstein and Wilson, 2005; Tymanskyj et al., 2012). "
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    • "As mentioned earlier, despite these seemingly critical functions of tau, tau knockout mice are viable, fertile, and relatively normal, with no signs of neurodegeneration. Furthermore, knockdown of tau with siRNA does not kill primary neurons in culture or prevent axon formation [61]. Thus, tau is not essential to neurons or to microtubules, likely due to compensation by and/or redundant functions of other proteins. "
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    12/2012; 2012(4):796024. DOI:10.6064/2012/796024
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    • "For RNAi-based depletion of kinesin-6 from cultured neurons, we used an siRNA SMARTpool as in our previous studies with other molecular motors (He et al., 2005; Myers and Baas, 2007; Nadar et al., 2008; Liu et al., 2010), traditional microtubule-associated proteins (Qiang et al., 2006), microtubule-severing proteins (Qiang et al., 2010) and doublecortin (Tint et al., 2009). For this approach, the siRNA is introduced by electroporation (using the Amaxa Nucleofector) into dissociated cells prior to plating as a mixture of four different sequences specific to the target gene. "
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