Comments on: Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels

I made some comments on this article for F1000Prime. The original evaluation can be found at: http://f1000.com/prime/718009660
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he DOI for the original post is 10.3410/f.718009660.793476858

M Zanic, PO Widlund, AA Hyman and J Howard (2013) Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels.
Nat Cell Biol  DOI: 10.1038/ncb2744
PMID: 23666085

This article provides clear insight into how microtubule polymerization rates are achieved in vivo. Rates from assays of in vitro microtubule polymerization are typically slow. Here, the authors achieve in vitro rates of up to 20 μm .min¯¹, which is around the highest that is seen in live cells. The key seems to be an allosteric interaction between the microtubule polymerase XMAP215 and the plus-end binding protein EB1. It is interesting to see that this interaction is not a conventional EB1-directed plus-end binding event but is, in fact, allosteric with the combination of EB1 and XMAP215 promoting polymerization. Using mathematical modelling, the authors also suggest that this synergistic step is in the final addition of the tubulin dimer to the existing lattice, an isomerization step where a loosely bound dimer becomes tightly bound. This work also contrasts with other work reconstituting the Drosophila microtubule polymerization machinery which implicated another protein, Sentin, in this process of rapid microtubule polymerization {1}. The data presented in this paper do not support a role for Sentin in the vertebrate system described here. The definition of the minimal components needed for rapid microtubule growth now provides the opportunity to integrate other components of the regulatory network controlling microtubule dynamics to provide a complete picture of the control of this process.

References:
{1} Reconstitution of dynamic microtubules with Drosophila XMAP215, EB1, and Sentin.
Li W, Moriwaki T, Tani T, Watanabe T, Kaibuchi K, Goshima G.
J Cell Biol 2012 Nov 26; 199(5):849-62PMID: 23185033 DOI: 10.1083/jcb.201206101

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