Overview

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.

Procedure

Cells migrate by extending membrane protrusions at the leading edge of the cell and retracting the membrane at the trailing edge of the cell, thus, pushing the cell forward.

These protrusion and retraction forces are generated mainly by the motor protein myosin-II.

Its globular head regions bind filamentous actin and use energy from ATP hydrolysis to pull and contract the actin bundles.

For example, at the lamellipodial front, a type of membrane protrusion, the myosin contracts the actin filaments anchored to cell-matrix junctions.

This increased mechanical stress strengthens the junction, thus forming mature focal adhesions.

These anchorage points produce traction forces on the substratum, pushing the cell forward.

At the rear end of lamellipodia, the bipolar myosin binds actin and bridges the branched filaments.

Then, the myosin heads pull the actin filaments and reorient them parallel to the lamellipodial front, retracting the sides of the cell.

This retraction directs the rear of the cell to follow the lamellipodial front, resulting in directed cell migration.