Non-muscle myosin II takes centre stage in cell adhesion and migration

Abstract

Non-muscle myosin II (NM II) is a hexameric actin-binding protein that is formed of two heavy chains, two essential light chains and two regulatory light chains. Its conformation and function are controlled by phosphorylation of the regulatory light chains and self-assembly into myosin filaments. NM II heavy chains interact through their coiled-coil domains and contain actin-binding and ATPase activities in their head domains. The essential light chains stabilize myosin structure and the regulatory light chains regulate the ATPase activity of NM II. There are three NM II heavy chain isoforms in mammals. These determine the NM II isoforms (NM IIA, NM IIB and NM IIC), which have unique kinetic properties and both specific and overlapping cellular functions. NM II controls cell protrusion, adhesion and polarity through its actin cross-linking and contractile properties. The three isoforms control different aspects of these processes. Myosin activation is regulated by adhesive signalling, which in turn is regulated by the action of myosin on actin organization and contraction though a poorly characterized feedback loop. There are several monogenic human disease syndromes caused by mutations of NM IIA and NM IIC that impair their enzymatic motor activity and ability to self-assemble.