Systematic genetic analysis of muscle morphogenesis and function in Drosophila

Schnorrer, Frank; Schönbauer, Cornelia; Langer, Christoph C. H.; Dietzl, Georg; Novatchkova, Maria; Schernhuber, Katharina; Fellner, Michaela; Azaryan, Anna; Radolf, Martin; Stark, Alexander; Keleman, Krystyna; Dickson, Barry J.

doi:10.1038/nature08799

Cited by 267 publications

(318 citation statements)

References 26 publications

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“…The Mef2-GAL4 driver line was crossed with two different UAS lines: UAS-mask(ex1)-IR targeting exon 1, which encodes the N-terminal region of the gene, and UAS-mask(ex6)-IR targeting exon 6, which encodes six of the N-terminal ankyrin repeats. The flightless phenotype of the UASmask(ex1)-IR line was previously identified in a screen for flightlessness in siRNA mutants (Schnorrer et al, 2010). Most of the UAS-mask(ex1)-IR flies driven by Mef2-GAL4 at 29°C did not eclose (88% died as late pupae and 12% eclosed but were flightless).…”

Section: Identification Of a Binding Partner Of Kin2mentioning

confidence: 99%

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

Katzemich

West

Fukuzawa

et al. 2015

Journal of Cell Science

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Drosophila obscurin (Unc-89) is a titin-like protein in the M-line of the muscle sarcomere. Obscurin has two kinase domains near the C-terminus, both of which are predicted to be inactive. We have identified proteins binding to the kinase domains. Kinase domain 1 bound Bällchen (Ball, an active kinase), and both kinase domains 1 and 2 bound MASK (a 400-kDa protein with ankyrin repeats). Ball was present in the Z-disc and M-line of the indirect flight muscle (IFM) and was diffusely distributed in the sarcomere. MASK was present in both the M-line and the Z-disc. Reducing expression of Ball or MASK by siRNA resulted in abnormalities in the IFM, including missing M-lines and multiple Z-discs. Obscurin was still present, suggesting that the kinase domains act as a scaffold binding Ball and MASK. Unlike obscurin in vertebrate skeletal muscle, Drosophila obscurin is necessary for the correct assembly of the IFM sarcomere. We show that Ball and MASK act downstream of obscurin, and both are needed for development of a well defined M-line and Z-disc. The proteins have not previously been identified in Drosophila muscle.

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Section: Identification Of a Binding Partner Of Kin2mentioning

confidence: 99%

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

Katzemich

West

Fukuzawa

et al. 2015

Journal of Cell Science

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“…Here, we extend the muscle analysis to the level of the sarcomere (Perkins et al, 2010;Schnorrer et al, 2010). Two titinlike proteins, Projectin and Kettin (Sallimus -FlyBase), form the connecting filaments in indirect flight muscles (IFMs) that link the Z-bands to thick filaments and function in muscle elasticity during oscillatory work in flight (Lakey et al, 1990;Moore et al, 1999;Ayme-Southgate et al, 2005;Bullard et al, 2006).…”

Section: Establishment Of a Dystrophic Myofibril Phenotypementioning

confidence: 99%

Genetic elevation of Sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila

et al. 2013

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SUMMARYDuchenne muscular dystrophy is a lethal genetic disease characterized by the loss of muscle integrity and function over time. Using Drosophila, we show that dystrophic muscle phenotypes can be significantly suppressed by a reduction of wunen, a homolog of lipid phosphate phosphatase 3, which in higher animals can dephosphorylate a range of phospholipids. Our suppression analyses include assessing the localization of Projectin protein, a titin homolog, in sarcomeres as well as muscle morphology and functional movement assays. We hypothesize that wunen-based suppression is through the elevation of the bioactive lipid Sphingosine 1-phosphate (S1P), which promotes cell proliferation and differentiation in many tissues, including muscle. We confirm the role of S1P in suppression by genetically altering S1P levels via reduction of S1P lyase (Sply) and by upregulating the serine palmitoyl-CoA transferase catalytic subunit gene lace, the first gene in the de novo sphingolipid biosynthetic pathway and find that these manipulations also reduce muscle degeneration. Furthermore, we show that reduction of spinster (which encodes a major facilitator family transporter, homologs of which in higher animals have been shown to transport S1P) can also suppress dystrophic muscle degeneration. Finally, administration to adult flies of pharmacological agents reported to elevate S1P signaling significantly suppresses dystrophic muscle phenotypes. Our data suggest that localized intracellular S1P elevation promotes the suppression of muscle wasting in flies.

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“…We therefore chose to pursue restricted tissue and developmental stage expression of UAS-based RNAinterference (RNAi) transgenes (Dietzl et al, 2007;Schnorrer et al, 2010), as an alternative method of disrupting gene activity during establishment of the adult fly musculature. To verify the usefulness of this approach in the context of adult myoblast fusion, we first assessed the effects of expressing UAS-Wsp-RNAi and UAS-D-WIP-RNAi constructs using the muscle-specific Mef2-GAL4 driver.…”

Section: Research Articlementioning

confidence: 99%

The actin nucleator WASp is required for myoblast fusion during adultDrosophilamyogenesis

et al. 2011

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SUMMARYMyoblast fusion provides a fundamental, conserved mechanism for muscle fiber growth. We demonstrate here that the functional contribution of Wsp, the Drosophila homolog of the conserved actin nucleation-promoting factor (NPF) WASp, is essential for myoblast fusion during the formation of muscles of the adult fly. Disruption of Wsp function results in complete arrest of myoblast fusion in all muscles examined. Wsp activity during adult Drosophila myogenesis is specifically required for muscle cell fusion and is crucial both for the formation of new muscle fibers and for the growth of muscles derived from persistent larval templates. Although Wsp is expressed both in fibers and individual myoblasts, its activity in either one of these cell types is sufficient. SCAR, a second major Arp2/3 NPF, is also required during adult myoblast fusion. Formation of fusionassociated actin 'foci' is dependent on Arp2/3 complex function, but appears to rely on a distinct, unknown nucleator. The comprehensive nature of these requirements identifies Arp2/3-based branched actin polymerization as a universal mechanism underlying myoblast fusion.

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Systematic genetic analysis of muscle morphogenesis and function in Drosophila

Cited by 267 publications

References 26 publications

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

Genetic elevation of Sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila

The actin nucleator WASp is required for myoblast fusion during adultDrosophilamyogenesis

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