and thin filaments like the sarcomeres of striated muscles, contraction is still due to the same sliding filament mechanism controlled by myosin crossbridges interacting with actin filaments. The thin filament of smooth muscle is made of actin, tropomyosin, caldesmon, and calmodulin. Within this type of muscle, caldesmon and calmodulin control the tropomyosin-mediated transition between on and off activity states. Caldesmon binds to actin, tropomyosin, calmodulin, and myosin, of which its interactions with actin are most important. The binding of caldesmon is strongly influenced by tropomyosin. Caldesmon is an inhibitor of actinomyosin ATPase and motility, and both actin binding and caldesmon inhibition are greatly enhanced in the presence of tropomyosin. Smooth muscle contraction is initiated by the release of Ca2+. Ca2+ binds to and activates calmodulin, which then binds to caldesmon. This binding causes the caldesmon protein to disengage from the actin filament, exposing the myosin-binding sites on the actin filament. Myosin motor heads are phosphorylated by myosin light-chain kinase, allowing the myosin head to interact with the actin filament and cause contraction. Role in cytoskeleton function The cytoskeleton is an elaborate network of filaments required for the proper functioning of a range of cellular processes including cell motility, cell division, intracellular trafficking, and the maintenance of cell shape. The cytoskeleton is composed of three distinct filament systems: microtubules, intermediate filaments, and microfilaments (also known as the actin cytoskeleton). It is the dynamic interactions between these filaments that provide cells with unique structures and functions. A number of regulatory mechanisms, employing many actin-binding proteins, have evolved to control the dynamics of the actin filament system. It is believed that tropomyosins play a pivotal role in this regulatory system, influencing the associations the actin filament has with other ABPs. Together, these associations confer specific properties on the filament, allowing these structures to be involved in a wide range of cellular processes, but also to rapidly respond to cellular stimuli. Role in diseases Cancer Many studies have shown that there are specific changes to the repertoire of tropomyosins expressed in cells that are undergoing cellular transformation. These highly reproducible results suggest that, during the process of cellular transformation, a process whereby a normal cell becomes malignant, there is a decreased synthesis of HMW tropomyosin isoforms. In the initial studies, transformation of rat embryo fibroblast cell line REF-52 and of normal rat kidney cells led to decreased synthesis of HMW tropomyosins. In both of