Abstract

Microtubules are dynamic polymers consisting of {beta}-tubulin heterodimers. The initial polymerization process, called microtubule nucleation, occurs spontaneously via {beta}-tubulin. Since a large energy barrier prevents microtubule nucleation in cells, the {gamma}-tubulin ring complex is recruited to the centrosome to overcome the nucleation barrier. However, detachment of a considerable number of microtubules from the centrosome is known to contribute to fundamental processes in cells. Here, we present evidence that minus-end-binding calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) serves as a strong nucleator for microtubule formation from soluble {beta}-tubulin independent of {gamma}-tubulin. CAMSAP2 significantly reduces the nucleation barrier close to the critical concentration for microtubule polymerization by stabilizing the longitudinal contacts among {beta}-tubulins. CAMSAP2 clusters together with {beta}-tubulin to generate nucleation intermediates, from which numerous microtubules radiate, forming aster-like structures. Our findings suggest that CAMSAP2 supports microtubule growth by organizing a nucleation centre as well as by stabilizing microtubule nucleation intermediates.