Abstract
Copyright: © 2012 Siddiqui MT. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Tropomyosin (TM) is a component of myofibrils, the contractile apparati of striated muscle cells. The assembly of a myofibril involves the precise ordering of several proteins into a linear array of sarcomeres. The process is complicated further because most of these proteins have multiple isoforms. Recent demonstration of the association of TM mutations with Hypertrophic Cardiomyopathy (HCM)/Familial Hypertrophic Cardiomyopathy (FHC) [1-3] or other cardiomyopathies such as Dilated Cardiomyopathy (DCM) [4,5] and nemalin skeletal myopathy [6] in humans have spurred renewed interest in the structural/functional relationships of TM. In vertebrate striated muscle, the thin filament consists largely of actin, TM, the Troponin (Tn) complex (Tn-I, Tn-C and Tn-T), Tropomodulin (Tmod), and Leiomodin (Lmod). It is responsible for mediating Ca+2 control of contraction and relaxation. With the influx of Ca+2 in muscle cells, troponin-C binds with Ca+2 and undergoes a rapid conformational change, which causes additional conformation changes in the TM-Tn complex exposing the myosin associated ATPase activity. As a result, the free myosin associated ATPase activity hydrolyzes ATP with the release of energy that helps muscle to contract. There are four genes (designated as TPM1, TPM2, TPM3, and TPM4) for TM in vertebrates [7,8] except for zebrafish where there are six TM genes [9], which generate a multitude of tissue and developmental specific isoforms through the use of different promoters, alternative mRNA splicing, and tissue specific translational control [10]. The functional significance of this diversity and how it may affect interactions with other sarcomeric proteins is not fully understood. Sarcomeric isoforms for both TPM1 and TPM2 are expressed in large mammals, including humans [11]. The protein of the sarcomeric isoform of TPM3 is not expressed in mammalian hearts. In mammals TPM4 is truncated relative to the gene found in avian [12] and amphibian species [13].
Highlights
Tropomyosin (TM) is a component of myofibrils, the contractile apparati of striated muscle cells
There are four genes for TM in vertebrates [7,8] except for zebrafish where there are six TM genes [9], which generate a multitude of tissue and developmental specific isoforms through the use of different promoters, alternative mRNA splicing, and tissue specific translational control [10]
Ectopic expression of TPM1α with various missense mutations implicated in human Familial Hypertrophic Cardiomyopathy (FHC) (e.g. D175, D180G, etc) [17,18] and in Dilated Cardiomyopathy (DCM) (E54K) in transgenic (TG) mice helped in developing mouse models for the diseases [19]
Summary
Tropomyosin (TM) is a component of myofibrils, the contractile apparati of striated muscle cells. The protein of the sarcomeric isoform of TPM3 is not expressed in mammalian hearts. TPM1α (one of the nine alternatively spliced isoforms of the TPM1 gene) has been identified as the major sarcomeric isoform in vertebrate hearts [8].
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