Neuron migration “under the wing” of Elongator

What is the follow-up scenario for “Elongator”?

As Alain Chariot describes it, “we could ask ourselves what interest Belgian researchers have in studying a neglected disease like familial dysautonomy, which does not concern any patients in Belgium.” But over and above the dysfunction of Elongator observed in some cases of that disease, the researchers actually were able to cast light on biological pathways that might turn out to be much more important. “So our real interest is to try to widen the physiological or physiopathological context of Elongator’s operation,” Chariot explained. “The invasive and metastatic ability of tumors, for example, requires an enormous amount of migration. How much is the Elongator complex involved in these migrations? This research is going on now,” said the “Signal transduction” specialist.

On another hand a deficit in the acetylation of alpha tubulin appears to be a molecular deficit common to neuro-degenerative diseases as different as familial dysautonomy, amyotrophic lateral sclerosis, and Huntington’s chorea. “Despite symptoms that are quite distinct, these diseases have points in common at the level of molecular deregulation. These very examples show how far problems with acetylation can be important in the progression of a whole series of pathologies,” Chariot said. Thus, beginning with the study of a dysfunction involving Elongator in persons suffering from familial dysautonomy, Alain Chariot and Laurent Nguyen traveled a long road in order to discover a link between the Elongator complex and the acetylation of alpha tubulin in microtubules, required for the rebuilding of the cytoskeleton of cells during their migrations.

An upcoming step in their research on Elongator will consist in identifying other substrates of the ELP3 sub-unit of the protein complex. “There are many proteins in cytoplasm that are acetylated and the function of their acetylation is not always well understood,” Nguyen emphasized. Another matter that will be taken up soon in the framework of this research: the migration of inhibitor neurons. “Interneurons use modes of migration that are completely different from the ones used by projection neurons. It would therefore be interesting to see if they exhibit similar problems when deprived of a functional Elongator complex,” he concluded. We can only hope that the study of “Elongator” ends up generating as many spinoffs as the “Terminator” did.

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