The β isotypes of tubulin in neuronal differentiation

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