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J Cell Sci. 1996 Feb;109 ( Pt 2):419-28.

Hysteretic behavior and differential apparent stability properties of microtubule species emerge from the regulation of post-translational modifications of microtubules.

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  • 1Service d'Imagerie Cellulaire, URA 1116 CNRS, Universit√© Paris-Sud, Orsay, France.


At the epigenetic level, microtubule diversity is generated by several mechanisms of reversible post-translational modifications of tubulin subunits. In most cases, modification enzymes preferentially act on the tubulin subunits of microtubules, whereas the substrate of the enzymes which ensure the reverse reaction is preferentially the alpha beta-dimer of nonpolymerized tubulin. Most modifications identified to date appear to be nearly ubiquitous within the animal kingdom. Moreover, modifications are generally not mutually exclusive, so that cellular microtubules often bear several distinct biochemical alterations whose biological role is yet unknown. Post-translational modifications often (but not always) occur on microtubule species with low turnover rate. However, in vitro comparison of the polymerization and depolymerization rates of modified or unmodified forms of tubulin did not reveal any significant difference between molecular species. Thus, post-translational modifications are thought to be the result rather than the cause of microtubule stability. We re-examine this contention in the light of a regulated kinetic scheme for multiple and non-exclusive enzymatic modifications of microtubules. This study shows that different apparent stability properties of microtubule species emerge under such a kinetic regulation, although all the species were assumed to have identical intrinsic stability properties. This model can be used to reinterpret the results of well-known studies bearing on the relationship between microtubule stability and post-translational modifications. Another important finding is that the existence of a regulation loop in one of the multiple pathways of enzymatic differentiation of microtubules endows the system with hysteretic properties. These properties may be viewed, under restrictive conditions, as a buffering mechanism for the transitions between microtubule growing and shrinking phases during fluctuations in the regulation of centrosomal nucleating activity.

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