Myoblast Fusion Requires Fibronectin Degradation by Exteriorized m-Calpain

Dourdin, Nathalie; Brustis, Jean-Jacques; Balcerzak, Denis; Elamrani, Najat; Poussard, Sylvie; Cottin, Patrick; Ducastaing, A.

doi:10.1006/excr.1997.3684

Cited by 54 publications

(40 citation statements)

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“…As both of these proteases are both present when myoblasts from C2C12 cells migrate, the existence of the two differential roles could be explained by a distinct localization of these enzymes in various cellular compartments . The capability of m-calpain to be exteriorized is now well established in several cell types such as myogenic cells as well as chondrocytes Dourdin et al, 1997;Szomor et al, 1999;Nishihara et al, 2001). Since this protease, located in the extracellular matrix, is capable of cleaving the fibronectin-integrin complexes at the time of fusion Dourdin et al, 1997;Pfaff et al, 1999), we suggest that m-calpain may regulate myoblast migration by this means.…”

Section: Discussionmentioning

confidence: 71%

“…The capability of m-calpain to be exteriorized is now well established in several cell types such as myogenic cells as well as chondrocytes Dourdin et al, 1997;Szomor et al, 1999;Nishihara et al, 2001). Since this protease, located in the extracellular matrix, is capable of cleaving the fibronectin-integrin complexes at the time of fusion Dourdin et al, 1997;Pfaff et al, 1999), we suggest that m-calpain may regulate myoblast migration by this means. However, our data obtained using a previously validated strategy (Dourdin et al, 1997) demonstrate that inhibition of only intracellular mcalpain is responsible for the reduced migration rate.…”

Section: Discussionmentioning

confidence: 71%

“…The calpain family is thought to be involved in a range of various diseases such as cataract formation, diabetes, rheumatoid arthritis, ischemia, neurodegenerative diseases and muscular dystrophies (David et al, 1993;Saito et al, 1993;Mouatt-Prigent et al, 1996;Hirsch et al, 1997;Ishikawa et al, 1999;Horikawa et al, 2000;Richard et al, 2000;Tidball and Spencer 2000;Tamada et al, 2001;Trumbeckaite et al, 2003). Moreover, calpains play pivotal roles in physiological and biological phenomena such as signal transduction, cell spreading and motility, apoptosis, regulation of cell cycle, and regulation of muscle cell differentiation (Huttenlocher et al, 1997;Potter et al, 1998;Villa et al, 1998;Atencio et al, 2000;Barnoy et al, 2000;Cottin et al, 2000;Patel and Lane, 2000;Dourdin et al, 2001;Glading et al, 2001;Sato and Kawashima, 2001). Concerning muscle cell differentiation, the calcium dependent proteolytic system has been identified as playing crucial roles during the earlier myogenesis steps, more particularly when the myoblasts fuse into multinucleated myotubes (Temm-Grove et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that these proteases can proteolyze many substrates such as myofibrillar proteins (such as troponin and alpha-actin) (Selliah et al, 1996;Mair, 1999) and cytoskeletal associated proteins (such as desmin, vimentin and talin) (Goll et al, 1991;Poussard et al, 1993;Dourdin et al, 1999). Moreover, exteriorization of m-calpain is required for myoblast fusion in order to hydrolyze extracellular matrix components or to cleave the linkage of fibronectin and integrins complexes (Brustis et al, 1993;Dourdin et al, 1997). Since myotube formation occurs by preliminary migratory events that permit the myoblast alignment and the two iso-enzymes are detectable at the myoblast stage, we have hypothesized that both ubiquitous calpain isoforms were involved in myoblast migration.…”

Section: Introductionmentioning

confidence: 99%

“…At these sites members of the calpain family probably cleave proteins involved in adhesion such as paxillin, alpha actinin, desmin, vimentin, talin, FAK (focal adhesion kinase) and cytosolic domain of b1-b3-integrins (Rees et al, 1990;Cooray et al, 1996;Meredith et al, 1998;Bhatt et al, 2002). Besides, treatments with specific calpain inhibitors or null mutation of capn4 in non-muscular cells induce a decrease of migration (Huttenlocher et al, 1997;Dourdin et al, 2001). Few studies suggested that inhibited calpain activity is associated to an increase of cell attachment (Huttenlocher et al, 1997) while other works indicated a drop in cell adhesion and a defect in focal adhesion formation (Kulkarni et al, 1999;Dedieu et al, 2003(b)).…”

Section: Introductionmentioning

confidence: 99%

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Myoblast migration is prevented by a calpain‐dependent accumulation of MARCKS

Dedieu

Mazères

Poussard

et al. 2003

Biology of the Cell

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Calpains, also called calcium activated neutral cysteine proteases are presently known to play pivotal roles in physiological and biological phenomena such as signal transduction, cell spreading and motility, apoptosis, regulation of cell cycle and regulation of muscle cell differentiation. Concerning this last point, calpains have been shown to play a crucial role during the earlier myogenesis. In this study we have analyzed the involvement of calpains during an important step of myogenesis: myoblast migration. Our findings show that myoblast migration was drastically reduced when the expression of µ-and m-calpain was decreased. We have also observed that MARCKS (myristoylated alanine rich C kinase substrate), a protein localized at focal adhesion sites, was significantly accumulated when the expression levels of calpains were decreased. Also, using phorbol myristate acetate, (an activator of PKC) and plasmids carrying the full-length cDNA of MARCKS or a cDNA fragment lacking the phosphorylation site domain, we demonstrated that normal myoblast migration is dependent on MARCKS phosphorylation and localization.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Myoblast migration is prevented by a calpain‐dependent accumulation of MARCKS

Dedieu

Mazères

Poussard

et al. 2003

Biology of the Cell

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Subcellular mobility of the calpain/calpastatin network: an organelle transient

2006

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Calpain (Cp) is a calcium (Ca(2+))-dependent cysteine protease. Activation of the major isoforms of Cp, CpI and CpII, are required for a number of important cellular processes including adherence, shape change and migration. The current concept that cytoplasmic Cp locates and associates with its regulatory subunit (Rs) and substrates as well as translocates throughout the cell via random diffusion is not compatible with the spatial and temporal constraints of cellular metabolism. The novel finding that Cp and Rs function relies upon tenacious hydrophobic interactions with organelle membranes offers a unifying explanation for the paradoxical and puzzling features of Cp activation and regulation such as how nM concentrations of intracellular Ca(2+) can activate Cp molecules requiring muM to mM concentrations of Ca(2+) for in vitro activation, and how this protease can spatially and temporally locate specific substrates and translocate throughout the cell. We hypothesize that Cp and its regulatory moieties associate with organelles to facilitate the activation of this protease resulting in the cleavage of substrates and aid in its translocation throughout the cell.

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Myoblast attachment and spreading are regulated by different patterns by ubiquitous calpains

Mazères¹,

Leloup²,

Daury³

et al. 2006

Cell Motil. Cytoskeleton

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The calcium-dependent proteolytic system is a large family of well-conserved ubiquitous and tissue-specific proteases, known as calpains, and an endogenous inhibitor, calpastatin. Ubiquitous calpains are involved in many physiological phenomena, such as the cell cycle, muscle cell differentiation, and cell migration. This study investigates the regulation of crucial steps of cell motility, myoblast adhesion and spreading, by calpains. Inhibition of each ubiquitous calpain isoform by antisense strategy pinpointed the involvement of each of these proteases in myoblast adhesion and spreading. Moreover, the actin cytoskeleton and microtubules were observed in transfected cells, demonstrating that each ubiquitous calpain could be involved in the actin fiber organization. C2C12 cells with reduced mu- or m-calpain levels have a rounded morphology and disorganized stress fibers, but no modification in the microtubule cytoskeleton. Antisense strategy directed against MARCKS, a calpain substrate during C2C12 migration, showed that this protein could play a role in stress fiber polymerization. A complementary proteomic analysis using C2C12 cells over-expressing calpastatin indicated that two proteins were under-expressed, while six, which are involved in the studied phenomena, were overexpressed after calpain inhibition. The possible role of these proteins in adhesion, spreading, and migration was discussed.

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Myoblast Fusion Requires Fibronectin Degradation by Exteriorized m-Calpain

Cited by 54 publications

References 0 publications

Myoblast migration is prevented by a calpain‐dependent accumulation of MARCKS

Myoblast migration is prevented by a calpain‐dependent accumulation of MARCKS

Subcellular mobility of the calpain/calpastatin network: an organelle transient

Myoblast attachment and spreading are regulated by different patterns by ubiquitous calpains

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