Cell–matrix interactions in muscle disease

Carmignac, Virginie; Durbeej, Madeleine

doi:10.1002/path.3020

Cited by 78 publications

(62 citation statements)

References 350 publications

(211 reference statements)

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“…For example, laminins (Lama2, Lama4) bind Itga7/b1 in the muscle basement membrane (Fig. 5) (Yurchenco et al, 2004;Durbeej, 2010;Carmignac and Durbeej, 2012), and defects in LAMA2 have been associated with merosin-deficient muscular dystrophy in humans (Tomé et al, 1994;Rooney et al, 2012). Furthermore, mutations that disrupt genes encoding crosslinking collagens (e.g.…”

Section: Integrin Signalingmentioning

confidence: 99%

Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix

2015

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Tendons and ligaments are extracellular matrix (ECM)-rich structures that interconnect muscles and bones. Recent work has shown how tendon fibroblasts (tenocytes) interact with muscles via the ECM to establish connectivity and strengthen attachments under tension. Similarly, ECM-dependent interactions between tenocytes and cartilage/bone ensure that tendon-bone attachments form with the appropriate strength for the force required. Recent studies have also established a close lineal relationship between tenocytes and skeletal progenitors, highlighting the fact that defects in signals modulated by the ECM can alter the balance between these fates, as occurs in calcifying tendinopathies associated with aging. The dynamic finetuning of tendon ECM composition and assembly thus gives rise to the remarkable characteristics of this unique tissue type. Here, we provide an overview of the functions of the ECM in tendon formation and maturation that attempts to integrate findings from developmental genetics with those of matrix biology.

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Section: Integrin Signalingmentioning

confidence: 99%

Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix

2015

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“…Mutations in most of the genes encoding components of the linkage complexes result in muscle disorders (Carmignac and Durbeej, 2012). In humans, mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies, whereas mutations in sarcoglycan genes are responsible for some forms of limb girdle muscular dystrophies (Cohn and Campbell, 2000).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of col22a1 gene in zebrafish induces a muscular dystrophy by disruption of the myotendinous junction

et al. 2013

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The myotendinous junction (MTJ) is the major site of force transfer in skeletal muscle, and defects in its structure correlate with a subset of muscular dystrophies. Col22a1 encodes the MTJ component collagen XXII, the function of which remains unknown. Here, we have cloned and characterized the zebrafish col22a1 gene and conducted morpholino-based loss-of-function studies in developing embryos. We showed that col22a1 transcripts localize at muscle ends when the MTJ forms and that COLXXII protein integrates the junctional extracellular matrix. Knockdown of COLXXII expression resulted in muscular dystrophy-like phenotype, including swimming impairment, curvature of embryo trunk/tail, strong reduction of twitch-contraction amplitude and contraction-induced muscle fiber detachment, and provoked significant activation of the survival factor Akt. Electron microscopy and immunofluorescence studies revealed that absence of COLXXII caused a strong reduction of MTJ folds and defects in myoseptal structure. These defects resulted in reduced contractile force and susceptibility of junctional extracellular matrix to rupture when subjected to repeated mechanical stress. Co-injection of subphenotypic doses of morpholinos against col22a1 and genes of the major muscle linkage systems showed a synergistic gene interaction between col22a1 and itga7 (α7β1 integrin) that was not observed with dag1 (dystroglycan). Finally, pertinent to a conserved role in humans, the dystrophic phenotype was rescued by microinjection of recombinant human COLXXII. Our findings indicate that COLXXII contributes to the stabilization of myotendinous junctions and strengthens skeletal muscle attachments during contractile activity.

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“…First, msk was uncovered in a genetic screen as a suppressor of a gain-of-function wing blistering phenotype caused by mutations in inflated (if), which encodes the aPS2 integrin subunit (Baker et al, 2002). Second, integrins are well characterized as the major receptor complex essential for both adhesion and signaling in muscle attachment (Carmignac and Durbeej, 2012;Bozyczko et al, 1989). Finally, both Dim7 and ElmoEDE become enriched at the sites of integrin localization in the MASs and this localization persists throughout active larval muscle contraction (Fig.…”

Section: Integrins Function Upstream Of Dim7-elmomentioning

confidence: 97%

Drosophila Importin-7 functions upstream of the Elmo signaling module to mediate the formation and stability of muscle attachments

Liu¹,

Odell²,

Geisbrecht³

2013

Journal of Cell Science

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SummaryEstablishment and maintenance of stable muscle attachments is essential for coordinated body movement. Studies in Drosophila have pioneered a molecular understanding of the morphological events in the conserved process of muscle attachment formation, including myofiber migration, muscle-tendon signaling, and stable junctional adhesion between muscle cells and their corresponding target insertion sites. In both Drosophila and vertebrate models, integrin complexes play a key role in the biogenesis and stability of muscle attachments through the interactions of integrins with extracellular matrix (ECM) ligands. We show that Drosophila importin-7 (Dim7) is an upstream regulator of the conserved Elmo-MbcRRac signaling pathway in the formation of embryonic muscle attachment sites (MASs). Dim7 is encoded by the moleskin (msk) locus and was identified as an Elmo-interacting protein. Both Dim7 and Elmo localize to the ends of myofibers coincident with the timing of muscle-tendon attachment in late myogenesis. Phenotypic analysis of elmo mutants reveal muscle attachment defects similar to those previously described for integrin mutants. Furthermore, Elmo and Dim7 interact both biochemically and genetically in the developing musculature. The muscle detachment phenotype resulting from mutations in the msk locus can be rescued by components in the Elmo signaling pathway, including the Elmo-Mbc complex, an activated Elmo variant, or a constitutively active form of Rac. In larval muscles, the localization of Dim7 and activated Elmo to the sites of muscle attachment is attenuated upon RNAi knockdown of integrin heterodimer complex components. Our results show that integrins function as upstream signals to mediate Dim7-Elmo enrichment to the MASs.

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Cell–matrix interactions in muscle disease

Cited by 78 publications

References 350 publications

Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix

Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix

Knockdown of col22a1 gene in zebrafish induces a muscular dystrophy by disruption of the myotendinous junction

Drosophila Importin-7 functions upstream of the Elmo signaling module to mediate the formation and stability of muscle attachments

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