Abnormal mitosis in cells adhering on an inactive integrin β results in binucleated cells.

Integrins are widely known for their adhesive and migratory functions. On page 491, Reverte et al. reveal that integrins are also needed for the microtubule assembly that makes cell division possible.

For many cell types, division does not occur unless the cells are stuck to a matrix. The blockade to division was first linked to integrins when it was discovered that cells do not enter S phase in response to growth factors unless integrins are engaged.

In the new report, the authors identify an inactive integrin β mutant that nevertheless supports entry into S phase. Once in mitosis, however, cells adhering via this mutant are unable to build a proper microtubule array. Although some cells had no spindle, others were multipolar. Most never completed cytokinesis, probably due to a defective spindle midzone, which helps to establish the cytokinetic furrow.

The cytoskeletal problems were not restricted to mitosis; interphase microtubule arrays were also disorganized, failing to radiate normally from centrosomes. In the mutants, the centrosomes did not coordinate microtubule regrowth in response to depolymerization. The faulty interphase array probably creates problems in transport and organelle positioning, but the authors have not yet examined these issues.

Ligation of the mutant integrin β with an activating antibody restored microtubule polymerization and cell division. The authors suppose that active integrins turn on downstream signaling molecules—perhaps kinases or small GTPases—that might help to stabilize microtubule networks or localize centrosomal proteins. They are currently narrowing down the possibilities by screening for signaling pathway inhibitors that mimic the integrin mutant. The end result might be a better understanding of how some cell types, such as tumor cells, bypass the need for adhesion during mitosis.