Transformation is an alternative to normal skeletal muscle development

Kaufman, Stephen J.; Parks, Christine M.; Bohn, J. G.; Faiman, Lia E.

doi:10.1016/0014-4827(80)90128-7

Cited by 39 publications

(19 citation statements)

References 47 publications

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“…This interesting finding is consistent with earlier results in which developmentally defective myogenic cells were shown to be transformed and tumorigenic (40) and did not express the H36 antigen (39) [later shown to be ␣ 7 -integrin (66)], and with the recent finding of a high rate of tumor formation in ␣ 7 -null mice (DJ Burkin, unpublished observations). Thus, enhancing the levels of ␣ 7 -integrin may also be useful as a therapeutic approach to cancer with minimal transcription effects.…”

Section: Discussionsupporting

confidence: 91%

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Liu

Burkin²,

Kaufman

2008

American Journal of Physiology-Cell Physiology

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Liu J, Burkin DJ, Kaufman SJ. Increasing ␣7␤1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression. Am J Physiol Cell Physiol 294: C627-C640, 2008. First published November 28, 2007 doi:10.1152/ajpcell.00329.2007.-The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The ␣ 7␤1-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of ␣ 7-integrin levels alleviates pathology in mdx/utrn Ϫ/Ϫ mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally compensate for the absence of dystrophin. To test whether increasing ␣ 7-integrin levels affects transcription and cellular functions, we generated ␣ 7-integrin-inducible C2C12 cells and transgenic mice that overexpress the integrin in skeletal muscle. C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to laminin, faster proliferation when serum was limited, resistance to staurosporine-induced apoptosis, and normal differentiation. Transgenic expression of eightfold more integrin in skeletal muscle did not result in notable toxic effects in vivo. Moreover, high levels of ␣ 7-integrin in both myoblasts and in skeletal muscle did not disrupt global gene expression profiles. Thus increasing integrin levels can compensate for defects in the extracellular matrix and cytoskeleton linkage caused by compromises in the dystrophin-glycoprotein complex without triggering apparent overt negative side effects. These results support the use of integrin enhancement as a therapy for muscular dystrophy. myoblast proliferation; integrin transgenic mice; microarray CELLS CAN RECOGNIZE AND INTERACT with their environment through membrane receptors specific for different extracellular matrix proteins. The heterodimeric integrins are evolutionarily conserved receptors for matrix proteins found in all metazoans (37). In skeletal muscle, the association of the extracellular matrix with the cytoskeleton is essential for maintaining the integrity of the sarcolemma, sustaining appropriate myofiber architecture, and correctly transmitting the forces produced by muscle contractions (5, 42). The ␣ 7 ␤ 1 -integrin is part of a linkage system that maintains such transmembrane associations in skeletal muscle (10,66). It binds to laminin in the basal lamina that surrounds muscle fibers. Within muscle fibers, the integrin associates with the subsarcolemmal cytoskeleton network through focal adhesion complexes (5). The ␣ 7 ␤ 1 -integrin is distributed along the sarcolemma at costameres, and it is also concentrated at neuromuscular and myotendinous junctions (2,48). This localization suggests that the integrin has a pivotal role in maintaining these specialized structures and their functions in skeletal muscle. Congenital myopathies caused by mutations in t...

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Section: Discussionsupporting

confidence: 91%

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Liu

Burkin²,

Kaufman

2008

American Journal of Physiology-Cell Physiology

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“…However, there appears to be a period in which these postmitotic, terminally differentiating myoblasts can be manipulated to replicate again (14,15): when replication is reinitiated, expression of the differentiated phenotype stops. Analysis of developmental mutants and the use of tumor viruses and growth factors likewise have led to the conclusion that continued proliferation is incompatible with terminal myogenic development (16)(17)(18)(19)(20)(21)(22)(23). Studies using heterokaryons suggest that soluble trans-acting factors may mediate or initiate terminal differentiation (24,25).…”

Section: Blastmentioning

confidence: 99%

Replicating myoblasts express a muscle-specific phenotype.

Kaufman

Foster²

1988

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

194

113

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During the terminal stage of skeletal myogenesis, myoblasts stop replicating, fuse to form multinucleate fibers, and express the genes that encode the proteins that convey contractile capacity. Because of this dramatic shift in proliferative state, morphology, and gene expression, it has been possible to readily identify and quantitate terminally differentiating myoblasts. In contrast, it is not clear whether the proliferating cells that give rise to postmitotic myoblasts are equally distinct in their phenotype and in fact whether distinct stages in skeletal myogenesis precede the onset of terminal differentiation. To address these questions, monoclonal antibodies and immunofluorescence microscopy were used to determine that replicating myoblasts from newborn rats do express a muscle-specific phenotype. To identify replicating cells, incorporation of 5-bromo-2'-deoxyuridine (BrdUrd) into DNA was assayed by using anti-BrdUrd antibody. The In what has come to be known as the terminal stage of skeletal muscle differentiation, myoblasts cease replicating and express a panoply of phenotypic characteristics intrinsic to this stage of development. During this same transition in myogenic development, skeletal myoblasts fuse to form multinucleate fibers in which assembly of myofibrillar proteins takes place. Once assembled in these fibers, these proteins provide the structural basis and enzymatic capacities that render the fibers functional contractile units, capable of responding to neuronal excitation. Expression of the genes that encode these proteins is largely regulated at the level of transcription (1-6); alternative splicing provides additional diversity and is often involved in the switching of isoforms (6, 7). Translation of muscle-specific transcripts may also be regulated (8-11).The earliest expression of the terminally differentiated phenotype takes place in myoblasts that normally do not replicate further (12, 13). However, there appears to be a period in which these postmitotic, terminally differentiating myoblasts can be manipulated to replicate again (14, 15): when replication is reinitiated, expression of the differentiated phenotype stops. Analysis of developmental mutants and the use of tumor viruses and growth factors likewise have led to the conclusion that continued proliferation is incompatible with terminal myogenic development (16-23). Studies using heterokaryons suggest that soluble trans-acting factors may mediate or initiate terminal differentiation (24,25). Transfection studies support this concept and indicate that the product of a single gene may mediate the onset of this stage of skeletal muscle development (26,27).By using antibodies and nucleic acid probes, and by measuring isozyme activities and myoblast fusion, it has been possible to identify and quantitate terminally differentiating myoblasts. In contrast, it is not clear whether the replicating cells that give rise to these postmitotic myoblasts have an equally distinct phenotype that distinguishes this particular stage of...

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“…Rat myogenic cells, L8 were derived by David Yaffe from embryonic (or newborn) rat hind limbs (Yaffe and Saxel, 1977). The L8E63 cells are a clone derived from the L8 cell line in the laboratory of Stephen Kaufman (Kaufman et al, 1980). L8E63 cells were grown in DMEM supplemented with 10% horse serum, penicillin, streptomycin, and 2 mM glutamine.…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Clathrin Isoform CHC22, a Component of Neuromuscular and Myotendinous Junctions, Binds Sorting Nexin 5 and Has Increased Expression during Myogenesis and Muscle Regeneration

Towler

Gleeson

Hoshino

et al. 2004

MBoC

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The muscle isoform of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear to be distinct from those of well-characterized clathrin-coated vesicles. In mature muscle CHC22 is preferentially concentrated at neuromuscular and myotendinous junctions, suggesting a role at sarcolemmal contacts with extracellular matrix. During myoblast differentiation, CHC22 expression is increased, initially localized with desmin and nestin and then preferentially segregated to the poles of fused myoblasts. CHC22 expression is also increased in regenerating muscle fibers with the same time course as embryonic myosin, indicating a role in muscle repair. CHC22 binds to sorting nexin 5 through a coiled-coil domain present in both partners, which is absent in CHC17 and coincides with the region on CHC17 that binds the regulatory light-chain subunit. These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions.

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Transformation is an alternative to normal skeletal muscle development

Cited by 39 publications

References 47 publications

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Replicating myoblasts express a muscle-specific phenotype.

Clathrin Isoform CHC22, a Component of Neuromuscular and Myotendinous Junctions, Binds Sorting Nexin 5 and Has Increased Expression during Myogenesis and Muscle Regeneration

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Transformation is an alternative to normal skeletal muscle development

Cited by 39 publications

References 47 publications

Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Replicating myoblasts express a muscle-specific phenotype.

Clathrin Isoform CHC22, a Component of Neuromuscular and Myotendinous Junctions, Binds Sorting Nexin 5 and Has Increased Expression during Myogenesis and Muscle Regeneration

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Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression