Potential role of tubulin acetylation and microtubule-based protein trafficking in familial dysautonomia.

Familial dysautonomia (FD), a disease of the autonomic and sensory nervous systems, involves mutations in the protein IkappaB kinase complex-associated protein, which is a component of the human Elongator acetylase complex. We suggest a hypothesis in which defects in tubulin acetylation and impairment of microtubule-based protein trafficking may be an underlying cause of FD. In addition, an Arabidopsis homolog of the Elongator subunit ELP3 has been found to bind to the alphabeta-tubulin heterodimer, suggesting that alpha-tubulin may be a cytoplasmic target of Elongator acetylase activity. Studies of synergistic double mutants in yeast indicate a novel role for Elongator in cytoskeletal dynamics, although this is probably because of an effect on actin rather than microtubules. Finally, we suggest that tubulin deacetylase inhibitors may prove useful in the treatment of FD.