The molecular and biochemical basis of Duchenne muscular dystrophy

Anderson, Marydilys S.; Kunkel, Louis M.

doi:10.1016/0968-0004(92)90437-e

Cited by 61 publications

(35 citation statements)

References 24 publications

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“…For example, in Duchenne muscular dystrophy, the loss of viable myofibrils is accompanied by an expansion of adipose mass within the muscle (22,23). A similar replacement of muscle mass by adipose cells is seen in mice carrying targeted disruptions of the myogenic bHLH proteins (24).…”

mentioning

confidence: 72%

Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha.

Tontonoz

Spiegelman

1995

Proc. Natl. Acad. Sci. U.S.A.

588

412

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Skeletal muscle and adipose tissue development often has a reciprocal relationship in vivo, particularly in myodystrophic states. We have investigated whether determined myoblasts with no inherent adipogenic potential can be induced to transdifferentiate into mature adipocytes by the ectopic expression of two adipogenic transcription factors, PPARy and C/EBPa. When cultured under optimal conditions for muscle differentiation, murine G8 myoblasts expressing PPARy and C/EBPa show markedly reduced levels of the myogenic basic helix-loop-helix proteins MyoD, myogenin, MRF4, and myf5 and are completely unable to differentiate into myotubes. Under conditions permissive for adipogenesis including a PPAR activator, these cells differentiate into mature adipocytes that express molecular markers characteristic of this lineage. Our results demonstrate that a developmental switch between these two related but highly specialized cell types can be controlled by the expression ofkey adipogenic transcription factors. These factors have an ability to inhibit myogenesis that is temporally and functionally separate from their ability to stimulate adipogenesis.

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mentioning

confidence: 72%

Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha.

Tontonoz

Spiegelman

1995

Proc. Natl. Acad. Sci. U.S.A.

588

412

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“…Defects in a nonerythroid spectrin from Drosophila are lethal and result in abnormal cell shape and aberrant epithelial organization (Lee et al, 1993). Defects in the spectrin-like molecule dystrophin are the cause of Duchenne muscular dystrophy (Anderson and Kunkel, 1992;Campbell, 1995). In each case, the membrane skeleton defect is thought to disrupt the mechanical properties of the plasma membrane.…”

Section: Introductionmentioning

confidence: 99%

Segregation of Two Spectrin Isoforms: Polarized Membrane-binding Sites Direct Polarized Membrane Skeleton Assembly

Dubreuil

Maddux

Grushko

et al. 1997

MBoC

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Spectrin isoforms are often segregated within specialized plasma membrane subdomains where they are thought to contribute to the development of cell surface polarity. It was previously shown that ankyrin and ␤ spectrin are recruited to sites of cell-cell contact in Drosophila S2 cells expressing the homophilic adhesion molecule neuroglian. Here, we show that neuroglian has no apparent effect on a second spectrin isoform (␣␤ H ), which is constitutively associated with the plasma membrane in S2 cells. Another membrane marker, the Na,K-ATPase, codistributes with ankyrin and ␣␤ spectrin at sites of neuroglian-mediated contact. The distributions of these markers in epithelial cells in vivo are consistent with the order of events observed in S2 cells. Neuroglian, ankyrin, ␣␤ spectrin, and the Na,K-ATPase colocalize at the lateral domain of salivary gland cells. In contrast, ␣␤ H spectrin is sorted to the apical domain of salivary gland and somatic follicle cells. Thus, the two spectrin isoforms respond independently to positional cues at the cell surface: in one case an apically sorted receptor and in the other case a locally activated cell-cell adhesion molecule. The results support a model in which the membrane skeleton behaves as a transducer of positional information within cells.

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“…It is caused by a defective gene that codes for a 427-kDa protein, dystrophin (1)(2)(3)(4)(5). The deduced amino acid sequence of dystrophin shows that it consists of four domains and suggests that it is a cytoskeletal protein (6).…”

mentioning

confidence: 99%

Dystrophin-related Protein in the Platelet Membrane Skeleton

Earnest¹,

Santos²,

Zuerbig³

et al. 1995

Journal of Biological Chemistry

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The platelet membrane is lined with a membrane skeleton that associates with transmembrane adhesion receptors and is thought to play a role in regulating the stability of the membrane, distribution and function of adhesive receptors, and adhesive receptor-induced transmembrane signaling. When platelets are lysed with Triton X-100, cytoplasmic actin filaments can be sedimented by centrifugation at low g-forces (15,600 ؋ g) but the membrane skeleton requires 100,000 ؋ g. The present study shows that DRP (dystrophin-related protein) sediments from lysed platelets along with membrane skeleton proteins. Sedimentation results from association with the membrane skeleton because DRP was released into the detergent-soluble fraction when actin filaments were depolymerized. Interaction of fibrinogen with the integrin ␣ IIb ␤ 3 induces platelet aggregation, transmembrane signaling, and the formation of integrin-rich cytoskeletal complexes that can be sedimented from detergent lysates at low g-forces. Like other membrane skeleton proteins, DRP redistributed from the high-speed pellet to the integrin-rich low-speed pellet of aggregating platelets. One of the signaling enzymes that is activated following ␣ IIb ␤ 3 -ligand interactions in a platelet aggregate is calpain; DRP was cleaved by calpain to generate a ϳ140-kDa fragment that remained associated with the low-speed detergent-insoluble fraction. These studies show that DRP is part of the platelet membrane skeleton and indicate that DRP participates in the cytoskeletal reorganizations resulting from signal transmission between extracellular adhesive ligand and the interior of the cell.Duchenne muscular dystrophy is one of the most common inherited human diseases. It is caused by a defective gene that codes for a 427-kDa protein, dystrophin (1-5). The deduced amino acid sequence of dystrophin shows that it consists of four domains and suggests that it is a cytoskeletal protein (6). The major rod-shaped domain contains 24 spectrin-like repeats. This domain is flanked on the amino terminus by a domain that has a high degree of homology to the actin-binding domains of spectrin and ␣-actinin, and on the carboxyl terminus by a cysteine-rich domain that shows some homology to a Ca 2ϩ -binding region in ␣-actinin. The most carboxyl-terminal end of dystrophin consists of a short domain that has no homology to any known protein and appears to play a role in linking the molecule to the plasma membrane (7,8). Recent studies using purified protein or recombinant fragments containing the putative actin-binding domain (9 -11) have shown that the protein can bind to actin filaments in vitro, supporting the idea that this molecule functions as a cytoskeletal protein. The finding that dystrophin exists in a submembranous location (8,12,13) and that the carboxyl-terminal end of the molecule associates tightly with a complex of membrane glycoproteins (termed dystroglycan) (14 -17) suggests that dystrophin is a component of a submembranous cytoskeleton.Although there is now considerable inform...

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The molecular and biochemical basis of Duchenne muscular dystrophy

Cited by 61 publications

References 24 publications

Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha.

Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha.

Segregation of Two Spectrin Isoforms: Polarized Membrane-binding Sites Direct Polarized Membrane Skeleton Assembly

Dystrophin-related Protein in the Platelet Membrane Skeleton

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