New aspects of tropomyosin-regulated neuritogenesis revealed by the deletion of Tm5NM1 and 2

Fath, Thomas; Chan, Yee-Ka Agnes; Vrhovski, Bernadette; Clarke, Hamish; Curthoys, Nikki M.; Hook, Jeffrey W.; Lemckert, Frances A.; Schevzov, Galina; Tam, Patrick; Watson, Catherine M.; Khoo, Poh-Lynn; Gunning, Peter W.

doi:10.1016/j.ejcb.2009.11.028

Cited by 31 publications

(38 citation statements)

References 39 publications

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“…26 We have previously demonstrated that although deletion of all cytoskeletal products from the γTm gene is lethal for embryonic development, 22 deletion of exon 9c-containing isoforms (Tm5NM4 and NM7) or exon 9d-containing isoforms (Tm5NM1 and NM2) leads to viable animals. 27,28 The importance of Tm gene products from the γTm gene during mammalian development has not been fully explored. 2).…”

Section: Resultsmentioning

confidence: 99%

“…Unlike our finding for the lethality caused by removing the γTm gene amino-terminal exon 1b, we have previously reported that removal of the carboxy-terminal exon 9c (129-Tpm3 tm1(neo;Δ9c)Pgun ) and exon 9d (129-Tpm3 tm1(neo;Δ9d)Pgun , B6-Tpm3 tm2(Δ9d)Pgun ) results in viable animals. 27,28 Subsequent breeding analysis of the Δ9d line is shown in table 3. The expected Mendelian ratios were not achieved, with significantly fewer (p < 0.05) than expected Δ9d -/-mice generated.…”

Section: Resultsmentioning

confidence: 99%

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Functional identity of the Gamma Tropomyosin gene

et al. 2011

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Functional identity of the Gamma Tropomyosin gene

et al. 2011

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“…All cell lines were propagated in 100 mm tissue culture dishes (Corning, New York, NY, USA) in high-glucose Dulbecco 0 s modied Eagle 0 s medium (Invitrogen, Carlsbad, CA, USA) containing 10% Hyclone-fetal bovine serum (Thermo Fisher Scientific, Waltham, MA, USA). The derivation of g-Tm knockout mouse lines and primary mouse embryo fibroblasts (MEF g-9DÀ/À) have been previously described (Fath et al, 2010). Cells were transiently transfected with cDNA expression plasmids encoding YFP-fused Tm5NM1 (previously described (Percival et al, 2004)), dominant-negative Rac GTPase (pGFP.RacN17, previously described (Bargon et al, 2005)) and LifeACT tagged with monomeric GFP to detect filamentous actin (generously provided by Roland Wedlich-Soldner, Max Planck Institute of Biochemistry).…”

Section: Methodsmentioning

confidence: 99%

The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility

et al. 2010

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Cell migration is an integral component of metastatic disease. The ability of cells to transit between mesenchymal and amoeboid modes of migration has complicated the development of successful therapies designed to target cell migration as a means of inhibiting metastasis. Therefore, investigations of the mechanisms that regulate cell migration and render cells stationary are necessary. Tropomyosins are actin-associating proteins that regulate the activity of several effectors of actin filament dynamics. Previously, we have shown that the tropomyosin isoform Tm5NM1 stabilizes actin filaments and inhibits cell migration in a two-dimensional culture system. Here, we show that Tm5NM1 inhibits the mesenchymal migration of multiple cell lines in an isoform-specific manner. Tm5NM1 stimulates the downregulation of Src kinase activity and a rounded or elliptical morphology in threedimensional collagen gels, and cells have dramatically reduced capacity to form pseudopodia. Importantly, we find that Tm5NM1 inhibits both the mesenchymal to amoeboid and amoeboid to mesenchymal transitions. Collectively, our data suggest that mimicking the action of Tm5NM1 overexpression represents an approach for effectively inhibiting the mesenchymal mode of migration.

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“…This isoform promotes increased axon length, growth cone size and dendritic branching, whereas expression of the non-neuronal Tpm1.7 (also known as Tm3) in neurons attenuates neurogenesis (Schevzov et al, 2005). By contrast, knockout of Tpm3.1 and Tpm3.2 (also known as Tm5NM2) resulted in a decrease in the size of growth cones with an increased rate of lamellipodia protrusions (Fath et al, 2010). Loss-offunction mutations in the Tm2 (also known as TmII) gene in Drosophila leads to cell autonomous expansion of neuronal dendritic fields (Li and Gao, 2003).…”

Section: Morphogenesismentioning

confidence: 99%

Tropomyosin – master regulator of actin filament function in the cytoskeleton

Gunning

Hardeman

Lappalainen

et al. 2015

Journal of Cell Science

225

228

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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.

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New aspects of tropomyosin-regulated neuritogenesis revealed by the deletion of Tm5NM1 and 2

Cited by 31 publications

References 39 publications

Functional identity of the Gamma Tropomyosin gene

Functional identity of the Gamma Tropomyosin gene

The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility

Tropomyosin – master regulator of actin filament function in the cytoskeleton

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