Mutations in the protein huntingtin that expand its N-terminal polyglutamine tract cause the inherited neurodegenerative disorder Huntington disease. The expanded polyglutamine repeat is thought to reduce the solubility of the protein, resulting in formation of the characteristic nuclear/perinuclear aggregates that probably cause neuronal cell death. Phillippe Djian and co-workers now show that huntingtin binds to microtubules. They demonstrate that the protein interacts specifically with β-tubulin(but not α-tubulin or MAP2) in lymphoblasts and brain. In addition, they demonstrate that it copurifies with polymerized microtubules in vitro and colocalizes with microtubules and centrosomes in vivo. This ability to associate with β-tubulin seems to be a property of both wild-type and mutant huntintin. The authors suggest that a high density of microtubules in the perinuclear region could make huntingtin aggregates more likely to develop in the perinuclear region. Since β-tubulin is more abundant in neurons than in any other cell type, such inclusions might form more rapidly in these cells.
