Tropomodulins and tropomyosins: working as a team

Colpan, Mert; Moroz, Natalia; Kostyukova, Alla S.

doi:10.1007/s10974-013-9349-6

Cited by 35 publications

(42 citation statements)

References 123 publications

(209 reference statements)

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“…Mutations in period P1, encoded by exon 1a in Tpm1.1 and 1b in Tpm3.1, have no observed effect on the function of either myosin (Figures 2 and 4). The first part encoded by exon 1 binds the C terminus of tropomyosin and tropomodulin (Colpan, Moroz, & Kostyukova, 2013), and includes an actin binding site (Barua et al, 2013), but the function of the second half, the site of the P1 mutations, is unknown.…”

Section: Tropomyosin Periods Encoded By Alternatively-expressed Exomentioning

confidence: 99%

Distinct sites in tropomyosin specify shared and isoform‐specific regulation of myosins II and V

et al. 2018

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Muscle contraction, cytokinesis, cellular movement, and intracellular transport depend on regulated actin-myosin interaction. Most actin filaments bind one or more isoform of tropomyosin, a coiled-coil protein that stabilizes the filaments and regulates interactions with other actin-binding proteins, including myosin. Isoform-specific allosteric regulation of muscle myosin II by actin-tropomyosin is well-established while that of processive myosins, such as myosin V, which transport organelles and macromolecules in the cell periphery, is less certain. Is the regulation by tropomyosin a universal mechanism, the consequence of the conserved periodic structures of tropomyosin, or is it the result of specialized interactions between particular isoforms of myosin and tropomyosin? Here, we show that striated muscle tropomyosin, Tpm1.1, inhibits fast skeletal muscle myosin II but not myosin Va. The non-muscle tropomyosin, Tpm3.1, in contrast, activates both myosins. To decipher the molecular basis of these opposing regulatory effects, we introduced mutations at conserved surface residues within the six periodic repeats (periods) of Tpm3.1, in positions homologous or analogous to those important for regulation of skeletal muscle myosin by Tpm1.1. We identified conserved residues in the internal periods of both tropomyosin isoforms that are important for the function of myosin Va and striated myosin II. Conserved residues in the internal and C-terminal periods that correspond to Tpm3.1-specific exons inhibit myosin Va but not myosin II function. These results suggest that tropomyosins may directly impact myosin function through both general and isoform-specific mechanisms that identify actin tracks for the recruitment and function of particular myosins.

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Section: Tropomyosin Periods Encoded By Alternatively-expressed Exomentioning

confidence: 99%

Distinct sites in tropomyosin specify shared and isoform‐specific regulation of myosins II and V

et al. 2018

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“…(B) Schematic of actin pointed-end capping by Tmod, modified from (Colpan et al, 2013) which was adapted from (Kostyukova et al, 2006). (C) Tmod structural domains and functional sites.…”

Section: Figurementioning

confidence: 99%

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Gray

Kostyukova

Fath

2017

Molecular and Cellular Neuroscience

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Actin is a profoundly influential protein; it impacts, among other processes, membrane morphology, cellular motility, and vesicle transport. Actin can polymerize into long filaments that push on membranes and provide support for intracellular transport. Actin filaments have polar ends: the fast-growing (barbed) end and the slow-growing (pointed) end. Depolymerization from the pointed end supplies monomers for further polymerization at the barbed end. Tropomodulins (Tmods) cap pointed ends by binding onto actin and tropomyosins (Tpms). Tmods and Tpms have been shown to regulate many cellular processes; however, very few studies have investigated their joint role in the nervous system. Recent data directly indicate that they can modulate neuronal morphology. Additional studies suggest that Tmod and Tpm impact molecular processes influential in synaptic signaling. To facilitate future research regarding their joint role in actin regulation in the nervous system, we will comprehensively discuss Tpm and Tmod and their known functions within molecular systems that influence neuronal development.

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“…Tropomodulin (Tmod), a 40-kDa tropomyosin (TM)-binding protein, caps the pointed ends of actin filaments (Weber et al 1994; Weber et al 1999). Tmods regulate actin dynamics in muscle and non-muscle cells by preventing the polymerization and depolymerization of actin filaments from the pointed ends (for reviews, see (Yamashiro et al 2012; Colpan et al 2013; Fath 2013)).…”

Section: Introductionmentioning

confidence: 99%

Tropomyosin-binding properties modulate competition between tropomodulin isoforms

Colpan

Moroz

Gray

et al. 2016

Archives of Biochemistry and Biophysics

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The formation and fine-tuning of cytoskeleton in cells are governed by proteins that influence actin filament dynamics. Tropomodulin (Tmod) regulates the length of actin filaments by capping the pointed ends in a tropomyosin (TM)-dependent manner. Tmod1, Tmod2 and Tmod3 are associated with the cytoskeleton of non-muscle cells and their expression has distinct consequences on cell morphology. To understand the molecular basis of differences in the function and localization of Tmod isoforms in a cell, we compared the actin filament-binding abilities of Tmod1, Tmod2 and Tmod3 in the presence of Tpm3.1, a non-muscle TM isoform. Tmod3 displayed preferential binding to actin filaments when competing with other isoforms. Mutating the second or both TM-binding sites of Tmod3 destroyed its preferential binding. Our findings clarify how Tmod1, Tmod2 and Tmod3 compete for binding actin filaments. Different binding mechanisms and strengths of Tmod isoforms for Tpm3.1 contribute to their divergent functional capabilities.

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Tropomodulins and tropomyosins: working as a team

Cited by 35 publications

References 123 publications

Distinct sites in tropomyosin specify shared and isoform‐specific regulation of myosins II and V

Distinct sites in tropomyosin specify shared and isoform‐specific regulation of myosins II and V

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Tropomyosin-binding properties modulate competition between tropomodulin isoforms

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