Tropomyosin has been implicated in the control of actin filament dynamics during cell migration, morphogenesis, and cytokinesis. In order to gain insight into the role of tropomyosins in cell division, we examined their expression in developing and neoplastic brain tissue. We found that the high-molecular-weight tropomyosins are downregulated at birth, which correlates with glial cell differentiation and withdrawal of most cells from the cell cycle. Expression of these isoforms was restricted to proliferative areas in the embryonic brain and was absent from the adult, where the majority of cells are quiescent. However, they were induced under conditions where glial cells became proliferative in response to injury. During cytokinesis, these tropomyosin isoforms were associated with the contractile ring. We also investigated tropomyosin expression in neoplastic CNS tissues. Low-grade astrocytic tumors expressed high-molecular-weight tropomyosins, while highly malignant CNS tumors of diverse origin did not (P = 0.001). Furthermore, high-molecular-weight tropomyosins were absent from the contractile ring in highly malignant astrocytoma cells. Our findings suggest a role for high-molecular-weight tropomyosins in astrocyte cytokinesis, although highly malignant CNS tumors are still able to undergo cell division in their absence. Additionally, the correlation between high-molecular-weight tropomyosin expression and tumor grade suggests that tropomyosins are potentially useful as indicators of CNS tumor grade.
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http://dx.doi.org/10.1002/glia.10174 | DOI Listing |
iScience
July 2022
Institute for Biophysical Chemistry, Fritz-Hartmann-Centre for Medical Research, Hannover Medical School, 30625 Hannover, Germany.
The effects of N-terminal acetylation of the high molecular weight tropomyosin isoforms Tpm1.6 and Tpm2.1 and the low molecular weight isoforms Tpm1.
View Article and Find Full Text PDFHum Mutat
September 2022
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nemaline myopathies (NEMs) are genetically and clinically heterogenous. Biallelic or monoallelic variants in TNNT1, encoding slow skeletal troponin T1 (TnT1), cause NEM. We report a 2-year-old patient and his mother carrying the heterozygous TNNT1 variant c.
View Article and Find Full Text PDFJ Neurooncol
January 2019
Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.
Introduction: The brain is a very soft tissue. Glioblastoma (GBM) brain tumours are highly infiltrative into the surrounding healthy brain tissue and invasion mechanisms that have been defined using rigid substrates therefore may not apply to GBM dissemination. GBMs characteristically lose expression of the high molecular weight tropomyosins, a class of actin-associating proteins and essential regulators of the actin stress fibres and focal adhesions that underpin cell migration on rigid substrates.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
October 2018
Laboratory of Gene Expression, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Tropomyosin isoforms contribute to generation of functionally divergent actin filaments. In the nematode Caenorhabditis elegans, multiple isoforms are produced from lev-11, the single tropomyosin gene, by combination of two separate promoters and alternative pre-mRNA splicing. In this study, we report that alternative splicing of lev-11 is regulated in a tissue-specific manner so that a particular tropomyosin isoform is expressed in each tissue.
View Article and Find Full Text PDFCurr Biol
July 2018
Cellular and Genetic Medicine Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address:
Tropomyosin proteins form stable coiled-coil dimers that polymerize along the α-helical groove of actin filaments [1]. The actin cytoskeleton consists of both co-polymers of actin and tropomyosin and polymers of tropomyosin-free actin [2]. The fundamental distinction between these two types of filaments is that tropomyosin determines the functional capability of actin filaments in an isoform-dependent manner [3-9].
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