ROLES OF ALPHA-ACTININ IN THE REGULATION OF MITOTIC SPINDLE ORGANIZATION IN MAMMALIAN CELLS

Abstract

Cytokinesis is the final step of cell division and is a tightly regulated spatio-temporal process. Proper positioning of the cleavage furrow requires microtubules including dynamic astral microtubules and stable equatorial microtubules. However, how these two populations of microtubules are regulated in a time and space dependent manner is not clearly understood. Earlier we had shown that over-expression of a-actinin an actin cross-linking protein increases the cortical stiffness of the cell and depletion of a-actinin leads to the formation of ectopic furrows. So, we next investigated the effect of depletion of a-actinin on microtubule organization during cytokinesis. Interesting we found depletion of a-actinin lead to the aberrant localization of centralspindlin, but not aurora B or PRC1, to the tips of astral microtubules which caused the stabilization of the astral microtubules. Depletion of a-actinin also caused impaired organization of midzone microtubules and relocation of aurora B from chromosomes to these microtubules, suggesting that ectopic recruitment of MKLP1 leads to a failure of assembly of midzone microtubules. Our findings unveil an unexpected yet crucial role for an actin crosslinking protein in the regulation of the localization of the microtubule-associated cytokinetic regulator.