The β Isotypes of Tubulin in Neuronal Differentiation

The differences among the vertebrate beta isotypes of tubulin are highly conserved in evolution, suggesting that they have functional significance. To address this, we have used differentiating neuroblastoma cells as a model system. These cells express the beta I, beta II, and beta III isotypes. Although there is no difference prior to differentiation, a striking difference is seen after differentiation. Both beta I and beta III occur in cell bodies and neurites, while beta II occurs mostly in neurites. Knocking down beta I causes a large decrease in cell viability while silencing beta II and beta III does not. Knocking down beta II causes a large decrease in neurite outgrowth without affecting viability. Knocking down beta III has little effect on neurite outgrowth and only decreases viability if cells are treated with glutamate and glycine, a combination known to generate free radicals and reactive oxygen species. It appears, therefore, that beta I is required for cell viability, beta II for neurite outgrowth and beta III for protection against free radicals and reactive oxygen species. (C) 2010 Wiley-Liss, Inc.