title: Tropomyosin-based regulation of the actin cytoskeleton in time and space.
abstract: Tropomyosins are rodlike coiled coil dimers that form continuous polymers along the major groove of most actin filaments. In striated muscle, tropomyosin regulates the actin-myosin interaction and, hence, contraction of muscle. Tropomyosin also contributes to most, if not all, functions of the actin cytoskeleton, and its role is essential for the viability of a wide range of organisms. The ability of tropomyosin to contribute to the many functions of the actin cytoskeleton is related to the temporal and spatial regulation of expression of tropomyosin isoforms. Qualitative and quantitative changes in tropomyosin isoform expression accompany morphogenesis in a range of cell types. The isoforms are segregated to different intracellular pools of actin filaments and confer different properties to these filaments. Mutations in tropomyosins are directly involved in cardiac and skeletal muscle diseases. Alterations in tropomyosin expression directly contribute to the growth and spread of cancer. The functional specificity of tropomyosins is related to the collaborative interactions of the isoforms with different actin binding proteins such as cofilin, gelsolin, Arp 2/3, myosin, caldesmon, and tropomodulin. It is proposed that local changes in signaling activity may be sufficient to drive the assembly of isoform-specific complexes at different intracellular sites.
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, and Muscle Development Unit, Children's Medical Research Institute, Westmead; New South Wales, Australia. peterg3@chw.edu.au
authors.forename: Peter
authors.initials: P
authors.lastname: Gunning
authors.forename: Geraldine
authors.initials: G
authors.lastname: O'Neill
authors.forename: Edna
authors.initials: E
authors.lastname: Hardeman
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000502:physiology; D000818:Animals; D003599:Cytoskeleton / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020033:Protein Isoforms; D015398:Signal Transduction / Q000502:physiology; D014335:Tropomyosin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D000199:Actins; D020033:Protein Isoforms; D014335:Tropomyosin