Tropomyosin – master regulator of actin filament function in the cytoskeleton

Abstract

Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual actin filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of actin filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal actin filament contains a homopolymer of Tpm homodimers, resulting in a filament of uniform Tpm composition along its length. Evidence for this 'master regulator' role is based on four core sets of observation. First, spatially and functionally distinct actin filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of actin filament nucleators can specify which Tpm isoform is added to the growing actin filament. Second, Tpms regulate wholeorganism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of actin filaments with myosin motors and actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of actin filament specified by their Tpm composition. This allows the cell to specify actin filament function in time and space by simply specifying their Tpm isoform composition.

A new isoform of Drosophila non-muscle Tropomyosin 1 interacts with Kinesin-1 and functions in oskar mRNA localization

“…In comparison to canonical Tropomyosins, Tm1C has a unique domain organization. Most tropomyosins, including the high-molecular-mass isoforms detected in mammals, are composed of coiled-coil domains that enable binding along the sides of actin filaments (Gunning et al, 2015). Interestingly, the high-molecularmass isoforms in mammalian cells are still less than 300 amino acids long.…”

“…Tropomyosins are actin-binding proteins that have a welldocumented role within muscle in mediating contraction (Gunning et al, 2015). However, non-muscle isoforms are also expressed and these function in a variety of actin-dependent processes (Manstein and Mulvihill, 2016).…”

Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs

“…In metazoans, actin filaments are usually formed as a copolymer with tropomyosin where the particular isoform of tropomyosin defines the functional properties of the filament (9). The tropomyosin isoform Tpm3.1 (previously known as Tm5NM1) is of particular interest as it is one of only two tropomyosins retained by essentially all tumor cells and is structurally divergent from the muscle tropomyosins (10,11).…”

Robust identification of Ptbp1-dependent splicing events by a junction-centric approach in Xenopus laevis

“…It is therefore highly encouraging to find that many Ptbp1-controlled genes that we discover are linked to cell shape or adhesion. Specifically, actn4 and tpm4 encode actinin alpha 4 (Murphy and Young, 2015) and tropomyosin 4 (Gunning et al, 2015), two cytoskeletal proteins that control the actin network. ITGA6 encodes integrin alpha 6, which plays a critical structural role in the hemidesmosome by its dimerisation with ITGB4, and human ITGA6 is a causal gene in epidermolysis bullosa with pyloric atresia (Schumann et al, 2013).…”