The cofactor-dependent pathways for alpha- and beta-tubulins in microtubule biogenesis are functionally different in fission yeast.

The biogenesis of microtubules in the cell comprises a series of complex steps, including protein-folding reactions catalyzed by chaperonins. In addition a group of evolutionarily conserved proteins, called cofactors (A to E), is required for the production of assembly-competent alpha-/beta-tubulin heterodimers. Using fission yeast, in which alp11(+), alp1(+), and alp21(+), encoding the homologs for cofactors B, D, and E, respectively, are essential for cell viability, we have undertaken the genetic analysis of alp31(+), the homolog of cofactor A. Gene disruption analysis shows that, unlike the three genes mentioned above, alp31(+) is dispensable for cell growth and division. Nonetheless, detailed analysis of alp31-deleted cells demonstrates that Alp31(A) is required for the maintenance of microtubule structures and, consequently, the proper control of growth polarity. alp31-deleted cells show genetic interactions with mutations in beta-tubulin, but not in alpha-tubulin. Budding yeast cofactor A homolog RBL2 is capable of suppressing the polarity defects of alp31-deleted cells. We conclude that the cofactor-dependent biogenesis of microtubules comprises an essential and a nonessential pathway, both of which are required for microtubule integrity.