Nemaline myopathy rod bodies

Yamaguchi, Mamoru; Robson, Richard M.; Stromer, Marvin H.; Dahl, David S.; Oda, Takuzo

doi:10.1016/0022-510x(82)90059-4

Cited by 57 publications

(11 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29) or whether other postmitotic cells (e.g., nerve cells) respond similarly. Although occasional nemaline bodies, or streaming Z-bands, appear in normal muscles (30)(31)(32), they are numerous and diagnostic of childhood-type nemaline myopathy (13,14). Serial biopsies from patients with this disease have shown that the bodies first appear as small clusters of normally spaced, but slightly enlarged, consecutive Z-bands that maintain continuity with flanking normal sarcomeres.…”

Section: Resultsmentioning

confidence: 99%

A sarcomeric alpha-actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes.

Schultheiss

Choi

Lin

et al. 1992

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

View full text Add to dashboard Cite

In many nonmuscle cells, nonsarcomeric a-actinin is distributed in the dense bodies of stress fibers, adhesion plaques, and adherens junctions. In-striated muscle, a sarcomeric isoform of a-actinin (s-a-wactlnn) Is found in the Z-bands of myofibrils and subsarcolemmal adhesion plaques. To understand the role(s) of the a-actinin isoforms in the assembly and maintenance of such cytoskeletal structures, full-length or truncated s-a-actinin cDNAs were expressed in PtK2 cells and in primary skeletal myogenic cells. We found the following. (i) In transfected PtK2 cells the truncated s-aactinin was rapidly incorporated into preexisting dense bodies, adhesion plaques, and adherens junctions. With time these structures collapsed, and the affected cells detached from the substrate. (ii) In myotubes the truncated s-a-actinin was incorporated into nascent Z-bands. Many of these progressively hypertrophied, forming nemaline-lke bodies. With time the affected myofibrils fagmented, and the myotubes detached from the substrate. (iii) In both cell types the truncated s-a-actinin was significntly more disruptive of the cytoskeletal structures than the full-length molecule. (iv) Pools of "overexpressed" full-length or truncated protein did not selfaggregate into homogeneous, amorphous complexes; rather the exogenous proteins selectively colocalized with the same cohort of cytoskeletal proteins with which the endogenous a-actinin normally associates. The similarity among the hypertrophied Z-bands in transfected myotubes, the nemaline bodies in patients with nemaline myopathies, and the streaming Z-bands seen in various muscle pathologies raises the possibility that the genetically determined nemaline bodies and the pathologically induced Z-band alterations may reflect primary and/or posttranslational modifications of s-a-actinin.a-Actinin appears to occupy a strategic role in the assembly and maintenance of stress fibers of nonmuscle cells and the myofibrils of muscle cells (1, 2). Two isoforms of a-actinin have been identified, a muscle-specific sarcomeric isoform, s-a-actinin, and a nonsarcomeric isoform, non-s-a-actinin (3-5). In cell-free systems, binding affinities have been demonstrated between both a-actinins and many of the proteins comprising stress fibers, myofibrils, and their respective membrane-attachment sites. Protein sequence analyses of the isoforms reveal a globular head that links actin filaments, a rod-shaped central portion thought important for anti-parallel dimer formation, and a carboxyl terminus with consensus sequences for two EF-hands with a calciumbinding potential (6-8).Cytoimmunofluorescence studies on nonmuscle cells have localized non-s-a-actinin to dense bodies in stress fibers and to the vinculin-positive adhesion plaques and adherens junctions into which stress fibers insert (9-11). Comparable studies on skeletal and cardiac cells have localized s-a-actinin to Z-bands in striated myofibrils, to precursor I-Z-I-like complexes in muscle undergoing myofibrillogenesis, and to vinculin-positive...

show abstract

Section: Resultsmentioning

confidence: 99%

A sarcomeric alpha-actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes.

Schultheiss

Choi

Lin

et al. 1992

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

View full text Add to dashboard Cite

show abstract

“…8 and 9). 216 Abnormal α‐actinin, though only in decreased amounts, has occasionally been seen in muscle specimens of patients with nemaline myopathy. 206, 209 Likewise, mutations in muscle‐related α‐actinins‐2 and ‐3 could not be identified in patients or families.…”

Section: Congenital Myopathies With Mutant Proteinsmentioning

confidence: 99%

Congenital myopathies at their molecular dawning

Goebel

2003

Muscle and Nerve

View full text Add to dashboard Cite

The introduction and application of molecular techniques have commenced to influence and alter the nosology of congenital myopathies. Long-known entities such as nemaline myopathies, core diseases, and desmin-related myopathies have now been found to be caused by unequivocal mutations. Several of these mutations and their genes have been identified by analyzing aggregates of proteins within muscle fibers as a morphological hallmark as in desminopathy and actinopathy, the latter a subtype among the nemaline myopathies. Immunohistochemistry has played a crucial role in recognizing this new group of protein aggregate myopathies within the spectrum of congenital myopathies. It is to be expected that other congenital myopathies marked by inclusion bodies may turn out to be such protein aggregate myopathies, depending on analysis of individual proteins within these protein aggregates and their association with putative gene mutations.

show abstract

“…These anomalous rod bodies, which appear in cardiac muscle with aging, in diseased skeletal muscle or can also be induced experimentally, are closely related to Z bands (Yamaguchi et al, 1982(Yamaguchi et al, , 1983b. Z rods…”

Section: Invertebrate Musclementioning

confidence: 99%

The muscle Z band: lessons in stress management

Vigoreaux

1994

J Muscle Res Cell Motil

105

View full text Add to dashboard Cite

Two of the most characteristic features of striated muscle are (i) its ability to contract and generate tension when activated and (ii) its ability to return to its original length and form after contraction or stretching ceases. These two properties are to a large extent the primary manifestations of separate sets of filament systems: contractile actin and myosin filaments and viscoelastic titin and intermediate filaments. Z bands function as a common link that mechanically integrates contractile and elastic elements and as such they play a fundamental role in transmission of active and passive forces. Differences in Z band structure have been described for distinct classes of muscle and fibre types. The diversity in Z band architecture has been built around its phylogenetically conserved role as an actin-anchoring structure. Novel proteins are likely to account for structural and functional differences seen across the phyla.

show abstract

Nemaline myopathy rod bodies

Cited by 57 publications

References 34 publications

A sarcomeric alpha-actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes.

A sarcomeric alpha-actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes.

Congenital myopathies at their molecular dawning

The muscle Z band: lessons in stress management

Contact Info

Product

Resources

About