Perturbing integrin function inhibits microtubule growth from centrosomes, spindle assembly, and cytokinesis

In many mammalian cell types, integrin-mediated cell-matrix adhesion is required for the G1-S transition of the cell cycle. As cells approach mitosis, a dramatic remodeling of their cytoskeleton accompanies dynamic changes in matrix adhesion, suggesting a mechanistic link. However, the role of integrins in cell division remains mostly unexplored. Using two cellular systems, we demonstrate that a point mutation in the beta 1 cytoplasmic domain (beta 1 tail) known to decrease integrin activity supports entry into mitosis but inhibits the assembly of a radial microtubule array focused at the centrosome during interphase, the formation of a bipolar spindle at mitosis and cytokinesis. These events are restored by externally activating the mutant integrin with specific antibodies. This is the first demonstration that the integrin beta 1 tail can regulate centrosome function, the assembly of the mitotic spindle, and cytokinesis.