AbstractThe neuronal microtubule‐associated protein tau has been implicated in the development of axonal morphology including the organization of microtubules into a uniformly oriented array of microtubules commonly referred to as “bundle.” Determination of the functional organization of tau has revealed that regions of tau protein which flank the microtubule‐binding domain affect the bundling of microtubules in vitro with a microtubule‐binding fragment of tau being most effective Brandt and Lee, 1993:J. Biol. Chem.268:3414‐3419. In order to study the relation of microtubule bundles that form in vitro to those observed in the axon, we determined the orientation of individual microtubules in bundles and the effects of bundling on microtubule assembly and stability in cell‐free assembly reactions. Here we report that bundles induced by a microtubule‐binding fragment of tau contain randomly oriented microtubules as determined by using the difference in growth rates at microtubule plus and minus ends. We demonstrate that in vitro bundling increases microtubule growth (about 30), stabilizes microtubules against dilution‐ and cold‐induced disassembly, and allows microtubule nucleation despite the absence of a tau region which has previously been shown to be required for tau‐dependent microtubule nucleation. We conclude that conditions that stabilize microtubules can lead to bundle formation and allow microtubule assembly by a mechanism different from that employed by microtubule‐associated proteins. The data also support the view that additional mechanisms besides the action of tau and tubulin exist in order to organize microtubules in the axon.
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