Merosin and laminin in myogenesis; specific requirement for merosin in myotube stability and survival
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Merosin and laminin in myogenesis; specific requirement for merosin in myotube stability and survival. / Vachon, P H; Loechel, F; Xu, H; Wewer, U M; Engvall, E.
I: Journal of Cell Biology, Bind 134, Nr. 6, 01.09.1996, s. 1483-97.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Merosin and laminin in myogenesis; specific requirement for merosin in myotube stability and survival
AU - Vachon, P H
AU - Loechel, F
AU - Xu, H
AU - Wewer, U M
AU - Engvall, E
PY - 1996/9/1
Y1 - 1996/9/1
N2 - Laminin (laminin-1; alpha 1-beta 1-gamma 1) is known to promote myoblast proliferation, fusion, and myotube formation. Merosin (laminin-2 and -4; alpha 2-beta 1/beta 2-gamma 1) is the predominant laminin variant in skeletal muscle basement membranes; genetic defects affecting its structure or expression are the causes of some types of congenital muscular dystrophy. However, the precise nature of the functions of merosin in muscle remain unknown. We have developed an in vitro system that exploits human RD and mouse C2C12 myoblastic cell lines and their clonal variants to study the roles of merosin and laminin in myogenesis. In the parental cells, which fuse efficiently to multinucleated myotubes, merosin expression is upregulated as a function of differentiation while laminin expression is downregulated. Cells from fusion-deficient clones do not express either protein, but laminin or merosin added to the culture medium induced their fusion. Clonal variants which fuse, but form unstable myotubes, express laminin but not merosin. Exogenous merosin converted these myotubes to a stable phenotype, while laminin had no effect. Myotube instability was corrected most efficiently by transfection of the merosin-deficient cells with the merosin alpha 2 chain cDNA. Finally, merosin appears to promote myotube stability by preventing apoptosis. Hence, these studies identify novel biological functions for merosin in myoblast fusion and muscle cell survival; furthermore, these explain some of the pathogenic events observed in congenital muscular dystrophy caused by merosin deficiency and provide in vitro models to further investigate the molecular mechanisms of this disease.
AB - Laminin (laminin-1; alpha 1-beta 1-gamma 1) is known to promote myoblast proliferation, fusion, and myotube formation. Merosin (laminin-2 and -4; alpha 2-beta 1/beta 2-gamma 1) is the predominant laminin variant in skeletal muscle basement membranes; genetic defects affecting its structure or expression are the causes of some types of congenital muscular dystrophy. However, the precise nature of the functions of merosin in muscle remain unknown. We have developed an in vitro system that exploits human RD and mouse C2C12 myoblastic cell lines and their clonal variants to study the roles of merosin and laminin in myogenesis. In the parental cells, which fuse efficiently to multinucleated myotubes, merosin expression is upregulated as a function of differentiation while laminin expression is downregulated. Cells from fusion-deficient clones do not express either protein, but laminin or merosin added to the culture medium induced their fusion. Clonal variants which fuse, but form unstable myotubes, express laminin but not merosin. Exogenous merosin converted these myotubes to a stable phenotype, while laminin had no effect. Myotube instability was corrected most efficiently by transfection of the merosin-deficient cells with the merosin alpha 2 chain cDNA. Finally, merosin appears to promote myotube stability by preventing apoptosis. Hence, these studies identify novel biological functions for merosin in myoblast fusion and muscle cell survival; furthermore, these explain some of the pathogenic events observed in congenital muscular dystrophy caused by merosin deficiency and provide in vitro models to further investigate the molecular mechanisms of this disease.
KW - Animals
KW - Apoptosis
KW - Base Sequence
KW - Cell Differentiation
KW - Cell Survival
KW - DNA, Complementary
KW - Gene Expression Regulation
KW - Humans
KW - Laminin
KW - Mice
KW - Molecular Sequence Data
KW - Muscle Fibers, Skeletal
KW - Muscular Dystrophy, Animal
KW - Rhabdomyosarcoma
KW - Transfection
KW - Tumor Cells, Cultured
M3 - Journal article
C2 - 8830776
VL - 134
SP - 1483
EP - 1497
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -
ID: 34326019