Lee et al. report that contractile myosin filaments bind guanine nucleotide exchange factors (GEFs) to prevent the activation of Rho family GTPases, potentially coordinating the dynamics of migrating cells.
Cells move by sending out adhesive protrusions at their leading edge, a process controlled by actin-regulating GTPases like Rac and Cdc42. Myosin II motors then contract the actin cytoskeleton to pull the rest of the cell forward. How the alternating protrusions and contractions are synchronized is unknown, but Lee et al. found a hint when they discovered that myosin II directly binds members of the Dbl family of GEFs.
Dbl GEFs preferentially bound myosin II assembled into actomyosin fibers, and interacted via their catalytic domains. The GEFs were thus inactive when associated with myosin filaments. Inhibiting myosin's contractile ATPase activity triggered their release, allowing them to activate GTPases and induce membrane protrusions. The motility-stimulating growth factor PDGF also liberated GEFs from myosin fibers, and blocking this release reduced PDGF-induced Rac activation and cytoskeletal rearrangements.
The interaction between myosin II and Dbl family GEFs could therefore coordinate contraction and protrusion. Senior author Eung-Gook Kim now wants to investigate whether migrating cells employ this mechanism by using biosensors to monitor where and when GTPases are activated in response to changes in myosin II contractility.
