Drosophila muscle myosin heavy chain encoded by a single gene in a cluster of muscle mutations

Bernstein, Sanford I.; Mogami, Kaname; Donady, J. James; Emerson, Charles P.

doi:10.1038/302393a0

Cited by 161 publications

(118 citation statements)

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“…More significantly, we can isolate other myosin isoforms by expressing them transgenically in the IFMs of mutant flies, Mhc 10 , which do not express the native IFM myosin. Myosin isoform differences do not appear to influence assembly properties (17,18).…”

Section: Discussionmentioning

confidence: 99%

“…Fifteen different MHC isoforms, arising from alternative splicing of mRNA transcripts from the single Mhc gene (10,11), have been found so far in a wide variety of muscle types, ranging from the supercontractile larval muscles to the highly ordered, asynchronous indirect flight muscles (IFMs) (12)(13)(14)(15). Four of the five alternatively spliced exon sets occur in the myosin head coding region and have been proposed to determine functional differences between isoforms ( Fig.…”

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confidence: 99%

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Alternative Exon-encoded Regions of Drosophila Myosin Heavy Chain Modulate ATPase Rates and Actin Sliding Velocity

Swank¹,

Bartoo

Knowles

et al. 2001

Journal of Biological Chemistry

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137

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To investigate the molecular functions of the regions encoded by alternative exons from the single Drosophila myosin heavy chain gene, we made the first kinetic measurements of two muscle myosin isoforms that differ in all alternative regions. Myosin was purified from the indirect flight muscles of wild-type and transgenic flies expressing a major embryonic isoform. The in vitro actin sliding velocity on the flight muscle isoform (6.4 m⅐s ؊1 at 22°C) is among the fastest reported for a type II myosin and was 9-fold faster than with the embryonic isoform. With smooth muscle tropomyosin bound to actin, the actin sliding velocity on the embryonic isoform increased 6-fold, whereas that on the flight muscle myosin slightly decreased. No difference in the step sizes of Drosophila and rabbit skeletal myosins were found using optical tweezers, suggesting that the slower in vitro velocity with the embryonic isoform is due to altered kinetics. Basal ATPase rates for flight muscle myosin are higher than those of embryonic and rabbit myosin. These differences explain why the embryonic myosin cannot functionally substitute in vivo for the native flight muscle isoform, and demonstrate that one or more of the five myosin heavy chain alternative exons must influence Drosophila myosin kinetics.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Alternative Exon-encoded Regions of Drosophila Myosin Heavy Chain Modulate ATPase Rates and Actin Sliding Velocity

Swank¹,

Bartoo

Knowles

et al. 2001

Journal of Biological Chemistry

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137

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“…Drosophila melanogaster; muscle; myosin heavy chain; transcription; enhancer; gene regulation Drosophila melanogaster is unusual in having a single muscle myosin heavy-chain gene (Mhc) (Bernstein et al, 1983;Rozek and Davidson, 1983), rather than a Mhc multigene family (see Emerson and Bernstein, 1987 for review). Alternative splicing of the primary transcripts from this gene yields multiple isoforms of the protein (Collier et al, 1990;George et al, 1989;Hastings and Emerson, 1991;Kazzaz and Rozek, 1989;Kronert et al, 1991;Zhang and Bernstein, 2001).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene

Hess

Singer

Trinh

et al. 2007

Gene Expression Patterns

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We show that a 2.6 kb fragment of the muscle myosin heavy-chain gene (Mhc) of Drosophila melanogaster (containing 458 base pairs of upstream sequence, the first exon, the first intron and the beginning of the second exon) drives expression in all muscles. Comparison of the minimal promoter to Mhc genes of ten Drosophila species identified putative regulatory elements in the upstream region and in the first intron. The first intron is required for expression in four small cells of the tergal depressor of the trochanter (jump) muscle and in the indirect flight muscle. The 3′ end of this intron is important for Mhc transcription in embryonic body wall muscle and contains AT-rich elements that are protected from DNase I digestion by nuclear proteins of Drosophila embryos. Sequences responsible for expression in embryonic, adult body wall and adult head muscles are present both within and outside the intron. Elements important for expression in leg muscles and in the large cells of the jump muscle flank the intron. We conclude that multiple transcriptional regulatory elements are responsible for Mhc expression in specific sets of Drosophila muscles. KeywordsDrosophila melanogaster; muscle; myosin heavy chain; transcription; enhancer; gene regulation Drosophila melanogaster is unusual in having a single muscle myosin heavy-chain gene (Mhc) (Bernstein et al., 1983;Rozek and Davidson, 1983), rather than a Mhc multigene family (see Emerson and Bernstein, 1987 for review). Alternative splicing of the primary transcripts from this gene yields multiple isoforms of the protein (Collier et al., 1990;George et al., 1989;Hastings and Emerson, 1991;Kazzaz and Rozek, 1989;Kronert et al., 1991;Zhang and Bernstein, 2001). Drosophila Mhc is expressed in all muscles at embryonic, larval, pupal and adult stages. Thus several stage-or muscle-specific enhancer elements may regulate its transcription.Transcriptional regulatory regions for a number of Drosophila muscle genes have been mapped, resulting in the identification of both unique and shared cis-acting elements (Arredondo et al., 2001;Kelly et al., 2002;Marin et al., 2004;Mas et al., 2004;Meredith and Storti, 1993). The latter includes E-boxes that bind helix-loop-helix transcription factors and MEF2 sites that bind MEF2 protein (Bour et al., 1995; Lilly et al., 1995). E-boxes, MEF2 sites and their binding factors positively regulate vertebrate muscle gene expression as well (see Molkentin and Olson, 1996 for review).* Corresponding author. Tel.: +1-619-594-5629; fax: +1-619-594-5676; E-mail address: sbernst@sunstroke.sdsu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal dis...

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“…Unlike all other organisms characterized to date, Drosophila melanogaster possesses a single muscle MHC gene (Bernstein et al 1983;Rozek and Davidson 1983). Alternative splicing of MHC transcripts results in the production of transcripts encoding different MHC iso forms (Bernstein et al 1986;Rozek and Davidson 1986;Wassenberg et al 1987;George et al 1989;Hess et al 1989).…”

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confidence: 99%

Ultrastructural and molecular analyses of homozygous-viable Drosophila melanogaster muscle mutants indicate there is a complex pattern of myosin heavy-chain isoform distribution.

O'Donnell¹,

Collier²,

Mogami³

et al. 1989

Genes Dev.

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We describe the ultrastructural and initial molecular characterization of four homozygous-viable, dominantflightless mutants of Drosophila melanogaster. Genetic mapping indicates that these mutations are inseparable from the known muscle myosin heavy-chain (MHC) allele Mhc^, and each mutation results in a muscle-specific reduction in MHC protein accumulation. The indirect flight muscles (IFMs) of each of these homozygous mutants fail to accumulate MHC, lack thick filaments, and do not display normal cylindrical myofibrils. As opposed to the null phenotype observed in the IFM, normal amounts of MHC accumulate in the leg muscles of three of these mutants, whereas the fourth mutant shows a 45% reduction in leg muscle MHC. The ultrastructure of the tergal depressor of the trochanter muscle (TDT, or jump muscle] is normal in one mutant, completely lacks thick filaments in a second mutant, and displays a reduction of thick filaments in two mutants. The thick filament reduction in this latter class of mutants is limited to the four smaller anterior cells of the TDT, indicating that the TDT is a mixed fiber-type muscle. Because all isoforms of muscle MHC are encoded by alternative splicing of transcripts from a single gene, our results suggest that there is a complex pattern of MHC isoform accumulation in Drosophila, The phenotypes of the homozygous-viable mutants provide evidence for the differential localization of MHC isoforms in different muscles, within the same muscle, and even within a single muscle cell. The mutant characteristics also suggest that the use of some alternative exons is shared among the IFM, TDT, and additional muscles whereas the use of others is unique to the IFM.[Key Words: Drosophila-, muscle mutants; myosin heavy chain; alternative RNA splicing]

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Drosophila muscle myosin heavy chain encoded by a single gene in a cluster of muscle mutations

Abstract: Drosophila muscle myosin heavy chain is encoded by a single-copy gene which is transcribed during both larval and adult development. This myosin gene maps to a chromosomal locus distant from any of the actin genes, but is within a cluster of flight muscle mutations.

Cited by 161 publications

References 40 publications

Alternative Exon-encoded Regions of Drosophila Myosin Heavy Chain Modulate ATPase Rates and Actin Sliding Velocity

Alternative Exon-encoded Regions of Drosophila Myosin Heavy Chain Modulate ATPase Rates and Actin Sliding Velocity

Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene

Ultrastructural and molecular analyses of homozygous-viable Drosophila melanogaster muscle mutants indicate there is a complex pattern of myosin heavy-chain isoform distribution.

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