Elongator and Alpha tubulin: a matter of acetylation

Elongator is known to act within cell nuclei to loosen the winding of DNA around histone proteins during transcription; this complex is primarily located in the cytoplasm. So, the two scientists began to look at proteins that Elongator was likely to acetylate within the cell membrane. “The best known protein in cytoplasm that can be acetylated is alpha tubulin,” noted Alain Chariot. This protein acts in the formation of microtubules, fibers that make up the cytoskeleton of a cell. Looking closer, the scientists observed that cells that had been deprived of ELP1 or ELP3 also had a reduced amount of acetylated alpha tubulin. In addition, “it is possible to extract enriched cellular fractions from microtubules, and when we performed this extraction it turned out that it was also enriched in Elongator. This proves that the complex has something to do with microtubules,” Chariot explained. Following this, in vitro experiments also provided confirmation of the involvement of the sub-unit ELP3 (part of Elongator) in the acetylation of alpha tubulin.

Finally, in order to confirm the link between the level of acetylation of alpha tubulin and the deficits in migration and branching of projection neurons, we replaced the natural form of alpha tubulin with a dominant negative form of that protein. That form could integrate into the microtubules, but unlike the natural form, it could not be acetylated, said Nguyen. “In the cells in which the natural form of alpha tubulin had been replaced by a dominant negative form, we observed deficits in migration and branching!”

Thus the cycle was confirmed: “The Elongator complex regulates the migration and branching of the progenitors of cortical neurons via the acetylation of alpha tubulin,” as stated in the very title of the publication by the two Liège scientists in the journal Cell. ”Beyond the implication of Elongator in cortical development, one of the very important features of this article is that up to now no acetylase of alpha tubulin had been discovered,” Nguyen said enthusiastically. The migration and branching of neurons requires a permanent remodeling of the cytoskeleton of cells during which microtubules act as guide rails to conduct various cellular elements to their proper destinations. The acetylation of alpha tubulin is thus crucial for the anchoring of molecular motors. “We can now imagine that a deficit in migration or branching might be caused by impaired movement of some cellular elements following insufficient acetylation of the alpha tubulin of some microtubules, that being caused by a non-function Elongator complex,” Nguyen continued.