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Publication Abstract from PubMed

Microtubules polymerize and depolymerize stochastically, a behavior essential for cell division, motility and differentiation. While many studies advanced our understanding of how microtubule-associated proteins tune microtubule dynamics in trans, we have yet to understand how tubulin genetic diversity regulates microtubule functions. The majority of in vitro dynamics studies are performed with tubulin purified from brain tissue. This preparation is not representative of tubulin found in many cell types. Here we report the 4.2A cryo-EM structure and in vitro dynamics parameters of alpha1B/betaI+betaIVb microtubules assembled from tubulin purified from a human embryonic kidney cell line with isoform composition characteristic of fibroblasts and many immortalized cell lines. We find that these microtubules grow faster and transition to depolymerization less frequently compared to brain microtubules. Cryo-EM reveals that the dynamic ends of alpha1B/betaI+betaIVb microtubules are less tapered and that these tubulin heterodimers display lower curvatures. Interestingly, analysis of EB1 distributions at dynamic ends suggests no differences in GTP cap sizes. Lastly, we show that the addition of recombinant alpha1A/betaIII tubulin, a neuronal isotype overexpressed in many tumors, proportionally tunes the dynamics of alpha1B/betaI+betaIVb microtubules. Our study is an important step towards understanding how tubulin isoform composition tunes microtubule dynamics.

Tubulin isoform composition tunes microtubule dynamics.,Vemu A, Atherton J, Spector JO, Moores CA, Roll-Mecak A Mol Biol Cell. 2017 Oct 11. pii: mbc.E17-02-0124. doi: 10.1091/mbc.E17-02-0124. PMID:29021343^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.