30.8: Role of Myosin in Cell Migration
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is this myosin-driven contraction of actin filaments and actin bundles that directs cell migration.
Myosin Promotes Adhesion
During cell migration, the lamellipodium at the cell front develops new focal adhesions that produce traction forces on the substratum. Studies have demonstrated that myosin is essential for the maturation of these adhesions, though the exact mechanism is not well understood. One hypothesis is that the myosin contractile force changes the conformation of cytoskeletal linker proteins, such as talin. This change exposes cryptic binding sites to actin and other linker proteins, thereby strengthening the adhesion. A second hypothesis states that adhesion proteins, such as integrins bound to actin, are clustered by the myosin-driven bundling of actin filaments. Thus, myosin-driven clustering of adhesion molecules, and changes in linker proteins, aid in the maturation of focal adhesions during cell migration.
Myosin and Organelle Positioning
Directional cell migration requires the establishment of cell polarity to determine the cell front and rear. In response to external stimuli, intracellular signaling cascades target various proteins, including myosin, to establish this polarity. Myosin is essential for repositioning the organelles, including the nucleus, Golgi apparatus, and the centrosomes, in alignment with the cell's polarity. For example, myosin anchors actin filaments around the nucleus by interacting with the linker protein nesprin embedded in the nuclear membrane. Thus, myosin helps to reposition the nucleus within the actin network as the cell changes shape during migration.
