title: Effect of Cardiomyopathic Mutations in Tropomyosin on Calcium Regulation of the Actin-Myosin Interaction in Skeletal Muscle.
abstract: Tropomyosin plays an important role in the regulation of actin-myosin interaction in striated muscles. Mutations in the tropomyosin gene disrupt actin-myosin interaction and lead to myopathies and cardiomyopathies. Tropomyosin with mutations in the α-chain is expressed in both the myocardium and skeletal muscles. We studied the effect of mutations in the α-chain of tropomyosin related to hypertrophic (D175N and E180G) and dilated cardiomyopathies (E40K and E54K) on calcium regulation of the actin-myosin interaction in skeletal muscles. We analyzed the calcium-dependent sliding velocity of reconstructed thin filaments containing F-actin, troponin, and tropomyosin over myosin surface in an in vitro motility assay. Mutations D175N and E180G in tropomyosin increased the sliding velocity and its calcium sensitivity, while mutation E40K reduced both these parameters. E54K mutation increased the sliding velocity of thin filaments, but did not affect its calcium sensitivity.
authors.affiliation: Institute of Immunology and Physiology, Ural Division of the Russian Academy of Sciences, Moscow, Russia. g_rodionova@mail.ru.
authors.forename: G V
authors.initials: GV
authors.lastname: Kopylova
authors.affiliation: Institute of Immunology and Physiology, Ural Division of the Russian Academy of Sciences, Moscow, Russia.
authors.forename: D V
authors.initials: DV
authors.lastname: Shchepkin
authors.affiliation: Institute of Immunology and Physiology, Ural Division of the Russian Academy of Sciences, Moscow, Russia.|B. N. Yeltsin Ural Federal University, Ekaterinburg, Russia.
authors.forename: D I
authors.initials: DI
authors.lastname: Borovkov
authors.affiliation: A. N. Bach Institute of Biochemistry, Federal Research Center of Biotechnology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: A M
authors.initials: AM
authors.lastname: Matyushenko
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D018482:Muscle, Skeletal / Q000737:chemistry / Q000502:physiology; D009154:Mutation; D009218:Myosins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012996:Solutions; D014335:Tropomyosin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014336:Troponin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D002021:Buffers; D011994:Recombinant Proteins; D012996:Solutions; C490775:TPM1 protein, human; D014335:Tropomyosin; D014336:Troponin; D009218:Myosins; D002118:Calcium
keywords: actin—myosin interaction; calcium regulation; in vitro motility assay; tropomyosin