Vicente-Manzanares et al. describe how myosin II isoforms ensure that a migrating cell knows its back from its front.
The leading edge of a migrating fibroblast is the site of rapid actin polymerization and adhesion turnover, whereas the rear of the cell contains stable actin bundles coupled to large adhesions. This polarized arrangement is controlled by myosin II, although how this motor protein and actin-crosslinker generates front–back asymmetry is unclear.
Vicente-Manzanares et al. found that one particular myosin II isoform—MIIA—initially specifies the cell rear by assembling actin clusters that the researchers called “proto-bundles.” But a different isoform—MIIB—was required to stabilize and enlarge these clusters into the actomyosin bundles typically found at the back of migrating fibroblasts. Microtubules weren't needed to form these bundles, but the leading edge was no longer positioned directly opposite the cell rear in the presence of the microtubule-depolymerizing drug nocodazole.
Cell-matrix adhesions associated with MIIB-dependent actin bundles were larger and more stable than adhesions at the cell front, but their adhesive signaling was suppressed. Key adaptor proteins like paxillin and p130(Cas) were largely unphosphorylated at rearward adhesions, and proteins that stimulate the small GTPase Rac weren't recruited as strongly, limiting actin polymerization and membrane protrusion at the cell rear. Rac was activated by adhesions at the cell front, however, in order to stimulate leading edge protrusion.
Author Miguel Vicente-Manzanares now wants to investigate how myosin II controls adhesive signaling. One explanation may be that it regulates the tension that adhesions are subjected to.
