Genetic suppression of phenotypes arising from mutations in dystrophin-related genes in Caenorhabditis elegans

Gieseler, Kathrin; Grisoni, Karine; Ségalat, Laurent

doi:10.1016/s0960-9822(00)00691-6

Cited by 91 publications

(110 citation statements)

References 28 publications

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“…These mutants undergo only slight muscle degeneration (Bessou et al, 1998;Grisoni et al, 2003). However, in a sensitized hlh-1(cc561) background, which is a mild mutation of the C. elegans homologue of the myogenic factor MyoD, dys-1 mutations lead to an extensive time-dependent muscle degeneration (Gieseler et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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DYC-1, a Protein Functionally Linked to Dystrophin inCaenorhabditis elegansIs Associated with the Dense Body, Where It Interacts with the Muscle LIM Domain Protein ZYX-1

Lecroisey

Martin

Mariol

et al. 2008

MBoC

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In Caenorhabditis elegans, mutations of the dystrophin homologue, dys-1, produce a peculiar behavioral phenotype (hyperactivity and a tendency to hypercontract). In a sensitized genetic background, dys-1 mutations also lead to muscle necrosis. The dyc-1 gene was previously identified in a genetic screen because its mutation leads to the same phenotype as dys-1, suggesting that the two genes are functionally linked. Here, we report the detailed characterization of the dyc-1 gene. dyc-1 encodes two isoforms, which are expressed in neurons and muscles. Isoform-specific RNAi experiments show that the absence of the muscle isoform, and not that of the neuronal isoform, is responsible for the dyc-1 mutant phenotype. In the sarcomere, the DYC-1 protein is localized at the edges of the dense body, the nematode muscle adhesion structure where actin filaments are anchored and linked to the sarcolemma. In yeast two-hybrid assays, DYC-1 interacts with ZYX-1, the homologue of the vertebrate focal adhesion LIM domain protein zyxin. ZYX-1 localizes at dense bodies and M-lines as well as in the nucleus of C. elegans striated muscles. The DYC-1 protein possesses a highly conserved 19 amino acid sequence, which is involved in the interaction with ZYX-1 and which is sufficient for addressing DYC-1 to the dense body. Altogether our findings indicate that DYC-1 may be involved in dense body function and stability. This, taken together with the functional link between the C. elegans DYC-1 and DYS-1 proteins, furthermore suggests a requirement of dystrophin function at this structure. As the dense body shares functional similarity with both the vertebrate Z-disk and the costamere, we therefore postulate that disruption of muscle cell adhesion structures might be the primary event of muscle degeneration occurring in the absence of dystrophin, in C. elegans as well as vertebrates.

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Section: Introductionmentioning

confidence: 99%

“…This study deals with the dyc-1 gene, which is of particular interest because its overexpression partially compensates for the absence of dystrophin in C. elegans dys-1; hlh-1 double mutants (Gieseler et al, 2000). The DYC-1 protein does not appear to have any particular motif that might help to understand its function.…”

Section: Introductionmentioning

confidence: 99%

DYC-1, a Protein Functionally Linked to Dystrophin inCaenorhabditis elegansIs Associated with the Dense Body, Where It Interacts with the Muscle LIM Domain Protein ZYX-1

Lecroisey

Martin

Mariol

et al. 2008

MBoC

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“…This speed and ease is, however, subject to a key limitation, sarcomeres containing GFP fusion proteins are not entirely normal 37 and therefore assessment of disrupted sarcomeres should be confirmed using additional more labor-intensive methods. These methods include use of polarized light 38 , phalloidin staining 39 , and indirect immunofluorescence 40 . Of these methods, only polarized light is relatively non-invasive; the other methods require fixation and therefore cannot be used in prospective studies of individual animals, rather they can only be used to confirm, cross sectionally, results from such studies.…”

Section: Imaging Of the Contractile Apparatusmentioning

confidence: 99%

Methods to Assess Subcellular Compartments of Muscle in <em>C. elegans</em>

Gaffney

Bass

Barratt

et al. 2014

JoVE

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Muscle is a dynamic tissue that responds to changes in nutrition, exercise, and disease state. The loss of muscle mass and function with disease and age are significant public health burdens. We currently understand little about the genetic regulation of muscle health with disease or age. The nematode C. elegans is an established model for understanding the genomic regulation of biological processes of interest. This worm's body wall muscles display a large degree of homology with the muscles of higher metazoan species. Since C. elegans is a transparent organism, the localization of GFP to mitochondria and sarcomeres allows visualization of these structures in vivo. Similarly, feeding animals cationic dyes, which accumulate based on the existence of a mitochondrial membrane potential, allows the assessment of mitochondrial function in vivo. These methods, as well as assessment of muscle protein homeostasis, are combined with assessment of whole animal muscle function, in the form of movement assays, to allow correlation of sub-cellular defects with functional measures of muscle performance. Thus, C. elegans provides a powerful platform with which to assess the impact of mutations, gene knockdown, and/or chemical compounds upon muscle structure and function. Lastly, as GFP, cationic dyes, and movement assays are assessed non-invasively, prospective studies of muscle structure and function can be conducted across the whole life course and this at present cannot be easily investigated in vivo in any other organism.

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“…Based on these similarities, a model of Duchenne's muscular dystrophy has been established in the nematode. Mutations in the dystrophin-like homologue, dys-1, when combined with a hypomorphic allele of the hlh-1 gene (MyoD homologue) result in progressive impairment of locomotion that leads to paralysis after the onset of adulthood (Gieseler et al, 2000). Locomotion defects are correlated with progressive muscle degeneration that occurs during animal ageing.…”

Section: Muscle Degenerationmentioning

confidence: 99%

Non‐apoptotic cell death in Caenorhabditis elegans

Vlachos

Tavernarakis

2010

Developmental Dynamics

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The simple nematode worm Caenorhabditis elegans has been instrumental in deciphering the molecular mechanisms underlying apoptosis. Beyond apoptosis, several paradigms of non-apoptotic cell death, either genetically or extrinsically triggered, have also been described in C. elegans. Remarkably, non-apoptotic cell death in worms and pathological cell death in humans share numerous key features and mechanistic aspects. Such commonalities suggest that similarly to apoptosis, non-apoptotic cell death mechanisms are also conserved, and render the worm a useful organism, in which to model and dissect human pathologies. Indeed, the genetic malleability and the sophisticated molecular tools available for C. elegans have contributed decisively to advance our understanding of non-apoptotic cell death. Here, we review the literature on the various types of non-apoptotic cell death in C. elegans and discuss the implications, relevant to pathological conditions in humans. Developmental Dynamics 239:1337-1351, 2010.V C 2010 Wiley-Liss, Inc.

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Genetic suppression of phenotypes arising from mutations in dystrophin-related genes in Caenorhabditis elegans

Abstract: As a C. elegans model for dystrophin-dependent myopathy, the dys-1; hlh-1 worms should permit the identification of genes, and ultimately drugs, that would reverse the muscle degeneration in this model.

Cited by 91 publications

References 28 publications

DYC-1, a Protein Functionally Linked to Dystrophin inCaenorhabditis elegansIs Associated with the Dense Body, Where It Interacts with the Muscle LIM Domain Protein ZYX-1

DYC-1, a Protein Functionally Linked to Dystrophin inCaenorhabditis elegansIs Associated with the Dense Body, Where It Interacts with the Muscle LIM Domain Protein ZYX-1

Methods to Assess Subcellular Compartments of Muscle in <em>C. elegans</em>

Non‐apoptotic cell death in Caenorhabditis elegans

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