Tropomyosin 3 Increases Striated Muscle Isoform Diversity

Abstract

Tropomyosin (TM), a component of the thin filament of the sarcomere, is encoded by a four-member multigene family: alpha-TM, beta-TM, TPM 3, and TPM 4. The alpha-TM, beta-TM, and TPM 3 genes each utilize an alternative splicing mechanism to encode a striated muscle isoform. Although the alpha-TM and beta-TM striated muscle isoforms are well characterized, relatively little is known about the TPM 3 isoform. We cloned and sequenced the murine TPM 3 cDNA and found that it exhibits a 93% nucleotide homology and 99% amino acid homology to the human sequence. Results show that, unlike humans, TPM 3 is not expressed in any developmental stage of murine hearts. TPM 3 message is expressed in slow-twitch skeletal muscle but is not found in representative fast-twitch musculature. The soleus, a representative slow-twitch muscle, expresses transcript levels of 65% beta-TM, 15% alpha-TM, and 20% TPM 3, but the TPM 3 protein accounts for approximately 31% of the total striated tropomyosin in slow-twitch muscle. In fast-twitch muscle, alpha-TM comprises 71% of the total striated muscle TM protein, and beta-TM comprises 29%. The results demonstrate that a translational mechanism regulates the production of the TM proteins, with beta-TM message not being efficiently translated. The unique distribution pattern of TPM 3 adds to the diversity of the tropomyosin family and strongly suggests functional significance for the different striated muscle TM isoforms.

Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles

“…Switching from ␣-TPM to TPM3 is associated with a decrease in myofilament Ca 2ϩ sensitivity and an attenuation of length-dependent activation (76). TPM3 isoform is predominantly found in the slow-twitch muscles (75), and the upregulation of TPM3 mRNA expression correlates with the increase in the number of slow fibers in denervated EDL muscles seen in the present study. The increased expression of ninjurin, neurofilament M, and NrCAM detected by the current study is most likely related to the Schwann cell remodeling after skeletal muscle denervation.…”

Differential Expression of Extracellular Matrix Proteins in Senescent and Young Human Fibroblasts: a Comparative Proteomics and Microarray Study

“…Four genes were selected based on the peptide counts (a large number) in the proteomic analysis and the availability of commercial antibodies. TPM3 is an example of a Class I gene (Pieples and Wieczorek, 2000). mRNA levels of TPM3 were elevated in senescent cells, while protein levels of TPM3 were also increased.…”

Patterns of tropomyosin and troponin-T isoform expression in jaw-closing muscles of mammals and reptiles that express masticatory myosin

“…However, two Tm characteristics have been consistently reported (e.g. Pieples and Wieczorek, 2000) since the original observations of Cummins and Perry (Cummins and Perry, 1973;Cummins and Perry, 1974): the amount of the electrophoretically faster migrating Tm-a is greater than the amount of Tm- in mammalian skeletal muscle, and the Tm-a/Tm- ratio is greater in mammalian fast compared with slow muscle. Therefore, based on electrophoretic mobility, it appears that Tm- is exclusively or predominantly expressed in some of the muscles examined (e.g.…”