Disease relevance of Tpm1

• Familial hypertrophic cardiomyopathy (HCM) can be caused by dominant missense mutations in cardiac troponin T (TnT), alpha-tropomyosin, C-protein, or cardiac myosin heavy chain genes [1].
• We mapped the functional domains encoded by the alpha-tropomyosin exon 9a (striated muscle-specific) and 9d (constitutively expressed), by measuring actin binding and regulation of the actomyosin MgATPase by tropomyosin exon 9 chimeras and truncation mutants expressed in E. coli [2].
• The thermal unfolding of the coiled-coil alpha-helix of recombinant alpha alpha-tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NS1 protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques [3].

High impact information on Tpm1

• Alternative splicing of alpha-tropomyosin pre-mRNA involves mutually exclusive utilization of exons 2 and 3, exon 3 being preferentially selected in most cells [4].
• Comparison of alpha-tropomyosin sequences from smooth and striated muscle [5].
• Here we report the nucleotide sequences of cloned complementary DNAs for rat striated and smooth muscle alpha-tropomyosin [5].
• We recently identified enhancer elements that activate the weak 3' splice site of alpha-tropomyosin exon 2 as well as a variety of heterologous weak 3' splice sites [6].
• We have used the rat alpha-tropomyosin gene as a model system of tissue-specific alternative splicing [7].

Biological context of Tpm1

• The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing [8].
• Alpha-tropomyosin gene organization. Alternative splicing of duplicated isotype-specific exons accounts for the production of smooth and striated muscle isoforms [9].
• Bacterially expressed alpha-tropomyosin lacks the amino-terminal acetylation present in muscle tropomyosin and binds poorly to actin (Hitchcock-DeGregori, S. E., and Heald, R. W. (1987) J. Biol. Chem. 262, 9730-9735) [10].
• Regulation of alternatively spliced alpha-tropomyosin gene expression by nerve extract [11].
• Mitogen-induced up-regulation of non-smooth muscle isoform of alpha-tropomyosin in rat aortic smooth muscle cells [12].

Anatomical context of Tpm1

• Four fibroblast tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene via alternative RNA splicing and the use of two promoters [13].
• Muscle cells were incubated with extracts prepared from neural tissue to investigate the mechanisms and factors which regulate mRNA transcript production of the alternatively spliced alpha-tropomyosin (alpha-TM) gene [11].
• Modulation of alpha-tropomyosin expression by alpha-tocopherol in rat vascular smooth muscle cells [14].

Associations of Tpm1 with chemical compounds

• Mutually exclusive splicing of alpha-tropomyosin exons enforced by an unusual lariat branch point location: implications for constitutive splicing [4].
• The cloned cells retained expression of functional surface receptors for angiotensin II, norepinephrine, and alpha-thrombin and high levels of the smooth muscle isoforms of alpha-actin, myosin heavy chain, myosin regulatory light chain, and alpha-tropomyosin mRNAs even after multiple passages [15].
• The solution structure of the functionally important N terminus of a short 247-residue non-muscle tropomyosin was determined in an engineered chimeric protein, GlyTM1bZip, consisting of the first 19 residues of rat short alpha-tropomyosin and the last 18 residues of the GCN4 leucine zipper [16].
• Effects of the state of the succinimido-ring on the fluorescence and structural properties of pyrene maleimide-labeled alpha alpha-tropomyosin [17].
• Among the cDNAs regulated by TGF-beta1 in C6 cells two cDNAs showed homology to alpha-tropomyosin and glycerol-3-phosphate dehydrogenase, respectively [18].

Other interactions of Tpm1

• In this manner, clones corresponding to myosin light chains 1, 2, and 3, troponin-C, troponin-T, alpha-tropomyosin, and alpha-actin were identified [19].
• We have used a novel gene transfer and selection strategy to detect a gene whose expression in fibroblasts is sufficient to switch them to smooth muscle-specific splicing of alpha-tropomyosin and also alpha-actinin [7].
• HP induced a significant increase in free androgen binding sites and a typical protein synthesis pattern characterized by a slow myosin light chain isozyme (LC-1S), an increase in fast isozymes (LC-1F,2F) and of beta-tropomyosin/alpha-tropomyosin ratio [20].

Analytical, diagnostic and therapeutic context of Tpm1

• Northern blot analyses with polyA+ RNA from juvenile heart suggest the presence of at least two different transcripts for alpha-tropomyosin in axolotl heart [21].
• Molecular cloning, sequencing and expression of an isoform of cardiac alpha-tropomyosin from the Mexican axolotl (Ambystoma mexicanum) [21].
• We used differential scanning calorimetry (DSC) and circular dichroism (CD) to investigate thermal unfolding of recombinant fibroblast isoforms of alpha-tropomyosin (Tm) in comparison with that of smooth muscle Tm [22].

References