Troponin of asynchronous flight muscle

Bullard, Belinda; Leonard, Kevin; Larkins, A. P.; Butcher, Geoffrey W.; Karlik, C C; Fyrberg, Eric

doi:10.1016/0022-2836(88)90360-9

Cited by 130 publications

(90 citation statements)

References 67 publications

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“…Electron microscopic examination of indirect flight muscle from the homozygous troponin I mutant demonstrated dramatically altered sarcomeric ultrastructure, consistent with prior studies (23,33). In contrast to the indirect flight muscle, the cardiac muscle of the homozygous troponin I mutant had more subtle effects on the thin and thick filaments.…”

Section: Discussionsupporting

confidence: 71%

Drosophila as a model for the identification of genes causing adult human heart disease

Wolf

Amrein

Izatt

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

233

226

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Drosophila melanogaster genetics provides the advantage of molecularly defined P-element insertions and deletions that span the entire genome. Although Drosophila has been extensively used as a model system to study heart development, it has not been used to dissect the genetics of adult human heart disease because of an inability to phenotype the adult fly heart in vivo. Here we report the development of a strategy to measure cardiac function in awake adult Drosophila that opens the field of Drosophila genetics to the study of human dilated cardiomyopathies. Through the application of optical coherence tomography, we accurately distinguish between normal and abnormal cardiac function based on measurements of internal cardiac chamber dimensions in vivo. Normal Drosophila have a fractional shortening of 87 ؎ 4%, whereas cardiomyopathic flies that contain a mutation in troponin I or tropomyosin show severe impairment of systolic function. To determine whether the fly can be used as a model system to recapitulate human dilated cardiomyopathy, we generated transgenic Drosophila with inducible cardiac expression of a mutant of human ␦-sarcoglycan (␦sg S151A ), which has previously been associated with familial dilated cardiomyopathy. Compared to transgenic flies overexpressing wild-type ␦sg, or the standard laboratory strain w 1118 , Drosophila expressing ␦sg S151A developed marked impairment of systolic function and significantly enlarged cardiac chambers. These data illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and the applicability of the vast genetic resources available in Drosophila to systematically study the genetic mechanisms responsible for human cardiac disease.optical coherence tomography ͉ cardiomyopathy

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Section: Discussionsupporting

confidence: 71%

Drosophila as a model for the identification of genes causing adult human heart disease

Wolf

Amrein

Izatt

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

233

226

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“…Troponin binding to the thin filament has been studied in nematode (Kimura et al, 1987), Limulus (Lehman, 1982), crab , scallop (Lehman, 1983a), and insect (Bullard et al, 1988;Newman et al, 1992;Reedy et al, 1994a;Wendt et al, 1997;Wendt and Leonard, 1999). This work has shown that troponin binds every 38-44 nm, as compared to 40 nm in vertebrates, but the large variety of preparation conditions again makes it difficult to interpret these differences.…”

Section: Thin Filamentmentioning

confidence: 99%

“…Lethocerus troponin T and troponin H (with Lethocerus tropomyosin) inhibit rabbit actomysoin, and rabbit troponin C relieves the inhibition if Ca ++ is present (Bullard et al, 1973a). Troponin H, although it replaces troponin I in asynchronous flight muscle, does not inhibit rabbit actomyosin ATPase activity (Bullard et al, 1988). Amino acids critical to Ca ++ -induced tropomyosin movement have been identified .…”

Section: Ecdysozoamentioning

confidence: 99%

Invertebrate muscles: Thin and thick filament structure; molecular basis of contraction and its regulation, catch and asynchronous muscle

Hooper

Hobbs

Thuma

2008

Progress in Neurobiology

131

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This is the second in a series of canonical reviews on invertebrate muscle. We cover here thin and thick filament structure, the molecular basis of force generation and its regulation, and two special properties of some invertebrate muscle, catch and asynchronous muscle. Invertebrate thin filaments resemble vertebrate thin filaments, although helix structure and tropomyosin arrangement show small differences. Invertebrate thick filaments, alternatively, are very different from vertebrate striated thick filaments and show great variation within invertebrates. Part of this diversity stems from variation in paramyosin content, which is greatly increased in very large diameter invertebrate thick filaments. Other of it arises from relatively small changes in filament backbone structure, which results in filaments with grossly similar myosin head placements (rotating crowns of heads every 14.5 nm) but large changes in detail (distances between heads in azimuthal registration varying from three to thousands of crowns). The lever arm basis of force generation is common to both vetebrates and invertebrates, and in some invertebrates this process is understood on the near atomic level. Invertebrate actomyosin is both thin (tropomyosin:troponin) and thick (primarily via direct Ca ++ binding to myosin) filament regulated, and most invertebrate muscles are dually regulated. These mechanisms are well understood on the molecular level, but the behavioral utility of dual regulation is less so. The phosphorylation state of the thick filament associated giant protein, twitchin, has been recently shown to be the molecular basis of catch. The molecular basis of the stretch activation underlying asynchronous muscle activity, however, remains unresolved.

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“…A reduction in stretch activation could be brought about by the reduced strain on a strain sensor in those peripheral filaments deficient in MLC-2. The strain sensor might be elastic connections between the thick filaments and the Z line (Auber and Couteaux, 1963;White, 1983;Nave and Weber, 1990) or t_roponin-H (Bullard et al, 1988).…”

Section: Relationship Of Flightlessness Wing Beat Frequency and Vismentioning

confidence: 99%

Myosin light chain-2 mutation affects flight, wing beat frequency, and indirect flight muscle contraction kinetics in Drosophila.

Warmke

Yamakawa

Molloy

et al. 1992

The Journal of Cell Biology

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Abstract. We have used a combination of classical genetic, molecular genetic, histological, biochemical, and biophysical techniques to identify and characterize a null mutation of the myosin light chain-2 (MLC-2) locus of Drosophila melanogaster. Mlc2 e3a is a null mutation of the MLC-2 gene resulting from a nonsense mutation at the tenth codon position. Mlc2 E3s confers dominant flightless behavior that is associated with reduced wing beat frequency. Mlc2 E3a heterozygotes exhibit a 50% reduction of MLC-2 mRNA concentration in adult thoracic musculature, which results in a commensurate reduction of MLC-2 protein in the indirect flight muscles. Indirect flight muscle myofibrils from Mlc2 ~38 heterozygotes are aberrant, exhibiting myofilaments in disarray at the periphery. Calcium-activated Triton X-100-treated single fiber segments exhibit slower contraction kinetics than wild type. Introduction of a transformed copy of the wild type MLC-2 gene rescues the dominant flightless behavior of Mlc2 E3s heterozygotes. Wing beat frequency and single fiber contraction kinetics of a representative rescued line are not significantly different from those of wild type. Together, these results indicate that wild type MLC-2 stoichiometry is required for normal indirect flight muscle assembly and function. Furthermore, these resuits suggest that the reduced wing beat frequency and possibly the flightless behavior conferred by Mlc2 e3s is due in part to slower contraction kinetics of sarcomeric regions devoid or partly deficient in MLC-2.F ORCE production in virtually all types of muscle requires the formation of mechanically strained, elastic cross-bridges between myosin-and actin-containing filaments. These cross-bridges are composed of the globular heads of the myosin heavy chain subunits and their associated light chains (the myosin alkali light chain and the myosin light chain-2 (MLC-2) t, the regulatory light chain). The myosin cross-bridge projects out from the thick (myosin) filament and attaches to an adjacent thin (actin) filament, activating an actomyosin Mg2 § which provides the chemical energy required for muscle contraction (Adelstein and Eisenberg, 1980). The cyclic making and breaking of these cross-bridges, together with a conformational change within the myosin molecule, causes the actin and myosin filaments to slide past each other enabling the muscle to shorten against an external load (Huxley, 1969 Two independent systems regulate the actomyosin ATPase cycle and contraction: a thin filament control system regulated by the troponin-tropomyosin complex, and a thick filament control system modulated by MLC-2 (Lehman and Szent-Gyorgyi, 1975;Sweeney and Stull, 1990, and references therein). The sophisticated molecular and genetic manipulations possible in Drosophila provides a powerful approach with which to investigate the structure-funodon relationships of these regulatory proteins (Peckham et al., 1990;Fyrberg and Beall, 1990). Our efforts have been directed toward defining the role of the MLC-2 protein.Her...

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Troponin of asynchronous flight muscle

Cited by 130 publications

References 67 publications

Drosophila as a model for the identification of genes causing adult human heart disease

Drosophila as a model for the identification of genes causing adult human heart disease

Invertebrate muscles: Thin and thick filament structure; molecular basis of contraction and its regulation, catch and asynchronous muscle

Myosin light chain-2 mutation affects flight, wing beat frequency, and indirect flight muscle contraction kinetics in Drosophila.

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