Sudarsan Rajan

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BACKGROUND Tropomyosin (TM), an essential actin-binding protein, is central to the control of calcium-regulated striated muscle contraction. Although TPM1alpha (also called alpha-TM) is the predominant TM isoform in human hearts, the precise TM isoform composition remains unclear. METHODS AND RESULTS In this study, we quantified for the first time the(More)
Mitochondrial permeability transition is a phenomenon in which the mitochondrial permeability transition pore (PTP) abruptly opens, resulting in mitochondrial membrane potential (ΔΨm) dissipation, loss of ATP production, and cell death. Several genetic candidates have been proposed to form the PTP complex, however, the core component is unknown. We(More)
Mutations in striated muscle alpha-tropomyosin (alpha-TM), an essential thin filament protein, cause both dilated cardiomyopathy (DCM) and familial hypertrophic cardiomyopathy. Two distinct point mutations within alpha-tropomyosin are associated with the development of DCM in humans: Glu40Lys and Glu54Lys. To investigate the functional consequences of(More)
Emerging findings suggest that two lineages of mitochondrial Ca(2+) uptake participate during active and resting states: 1) the major eukaryotic membrane potential-dependent mitochondrial Ca(2+) uniporter and 2) the evolutionarily conserved exchangers and solute carriers, which are also involved in ion transport. Although the influx of Ca(2+) across the(More)
Current electrophoretic methods have not been optimized to fully separate post-translationally modified mutant forms of tropomyosin (Tm) from wild-type cardiac samples. We describe here a method employing a modified 2-D PAGE/2-D DIGE protocol, to fully separate native, mutant (E54K), and phosphorylated forms of Tm. Our data demonstrate the first evidence of(More)
The ligand specificity of transforming growth factor beta (TGFbeta) in vivo in mouse cardiac cushion epithelial-to-mesenchymal transition (EMT) is poorly understood. To elucidate the function of TGFbeta in cushion EMT, we analyzed Tgfb1(-/-), Tgfb2(-/-), and Tgfb3(-/-) mice between embryonic day (E) 9.5 and E14.5 using both in vitro and in vivo approaches.(More)
Tropomyosin plays a key role in controlling calcium regulated sarcomeric contraction through its interactions with actin and the troponin complex. The focus of this review is on striated muscle tropomyosin isoforms and the in vivo approach we have taken to define the functional differences among these isoforms in regulating cardiac physiology. In addition,(More)
The existence of a feedback mechanism regulating the precise amounts of muscle structural proteins, such as actin and the actin-associated protein tropomyosin (Tm), in the sarcomeres of striated muscles is well established. However, the regulation of nonmuscle or cytoskeletal actin and Tms in nonmuscle cell structures has not been elucidated. Unlike the(More)
Tropomyosin (TM) is involved in Ca(2+)-mediated muscle contraction and relaxation in the heart. Striated muscle alpha-TM is the major isoform expressed in the heart. The expression of striated muscle beta-TM in the murine myocardium results in a decreased rate of relaxation and increased myofilament Ca(2+) sensitivity. Replacing the carboxyl terminus (amino(More)
α-Tropomyosin (α-TM) has a conserved, charged Asp-137 residue located in the hydrophobic core of its coiled-coil structure, which is unusual in that the residue is found at a position typically occupied by a hydrophobic residue. Asp-137 is thought to destabilize the coiled-coil and so impart structural flexibility to the molecule, which is believed to be(More)