The beta 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 betaI, betaII, and betaIII isotypes. Although there is no difference prior to differentiation, a striking difference is seen after differentiation. Both betaI and betaIII occur in cell bodies and neurites, while betaII occurs mostly in neurites. Knocking down betaI causes a large decrease in cell viability while silencing betaII and betaIII does not. Knocking down betaII causes a large decrease in neurite outgrowth without affecting viability. Knocking down betaIII 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 betaI is required for cell viability, betaII for neurite outgrowth and betaIII for protection against free radicals and reactive oxygen species.