Molecular Structure of Sarcomere-to-Membrane Attachment at M-Lines in<i>C. elegans</i>Muscle

Qadota, Hiroshi; Benian, Guy M.

doi:10.1155/2010/864749

Cited by 33 publications

(42 citation statements)

References 57 publications

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“…Many of the proteins of myofilaments, attachment structures, and regulators of contraction/relaxation have been identified through genetic and molecular biological analyses, and characterized cell biologically by using specific antibodies and GFP fusion proteins [Moerman and Fire, 1997; Qadota and Benian, 2010; Gieseler et al, 2016]. For C. elegans muscle, electron microscopy images are also available [Waterston et al, 1980; Zengel and Epstein, 1980; Waterston, 1988; Gieseler et al, 2016].…”

Section: Introductionmentioning

confidence: 99%

High‐resolution imaging of muscle attachment structures in Caenorhabditis elegans

et al. 2017

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We used structured illumination microscopy (SIM) to obtain super-resolution images of muscle attachment structures in C. elegans striated muscle. SIM imaging of M-line components revealed two patterns: PAT-3 (β-integrin) and proteins that interact in a complex with the cytoplasmic tail of β-integrin and localize to the basal muscle cell membrane (UNC-112 (kindlin), PAT-4 (ILK), UNC-97 (PINCH), PAT-6 (α-parvin) and UNC-95), are found in discrete, angled segments with gaps. In contrast, proteins localized throughout the depth of the M-line (UNC-89 (obscurin) and UNC-98) are imaged as continuous lines. Systematic immunostaining of muscle cell boundaries revealed that dense body components close to the basal muscle cell membrane also localize at cell boundaries. SIM imaging of muscle cell boundaries reveal “zipper-like” structures. Electron micrographs reveal electron dense material similar in appearance to dense bodies located adjacent to the basolateral cell membranes of adjacent muscle cells separated by ECM. Moreover, by EM, there are a variety of features of the muscle cell boundaries that help explain the zipper-like pattern of muscle protein localization observed by SIM. Short dense bodies in atn-1 mutants that are null for α-actinin and lack the deeper extensions of dense bodies, showed “zipper-like” structures by SIM similar to cell boundary structures, further indicating that the surface-proximal components of dense bodies form the “zipper-like” structures at cell boundaries. Moreover, mutants in thin and thick filament components do not have “dot-like” dense bodies, suggesting that myofilament tension is required for assembly or maintenance of proper dense body shape.

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Section: Introductionmentioning

confidence: 99%

High‐resolution imaging of muscle attachment structures in Caenorhabditis elegans

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“…The cytoplasmic tail of integrin is associated with a complex of four conserved proteins (UNC-112 (kindlin), PAT-4 (integrinlinked kinase (ILK) 3 ), PAT-6 (actopaxin), and UNC-97 (PINCH)) (9 -12). UNC-97 links to myosin in thick filaments through four different complexes: via UNC-98, via LIM-9 (FHL) and UNC-96, via LIM-8, and via UNC-95 and LIM-8 (13)(14)(15)(16).…”

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A Molecular Mechanism for the Requirement of PAT-4 (Integrin-linked Kinase (ILK)) for the Localization of UNC-112 (Kindlin) to Integrin Adhesion Sites

Qadota

Moerman

Benian

2012

Journal of Biological Chemistry

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Background: PAT-4 (ILK) is required for localization of UNC-112 (kindlin) to integrin adhesion sites. Results: N-and C-terminal halves of UNC-112 interact, and mutations abolishing this interaction restore the ability of a mutant UNC-112 that cannot bind PAT-4 to localize. Conclusion: UNC-112 exists in two conformations, and binding to PAT-4 converts UNC-112 to an open state. Significance: This molecular mechanism may be conserved among kindlins.

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“…During the past decade, at least 10 new sarcomeric proteins have been identified using screens of a yeast 2-hybrid library with baits consisting of known nematode sarcomeric proteins. 17 Homology to vertebrate muscle proteins identify at least another 2 dozen proteins. Thus, the 40 Unc, 20 Pat, 104 sarcomeredefective, 10 interacting, and 24 homologous proteins sum to a total of 198.…”

Section: Proteomes Of Nematodes and Human Heart Are Conservedmentioning

confidence: 99%

“…Nematode muscle M-lines and dense bodies not only serve the function of analogous structures in vertebrate muscle, but also are similar to the costameres of vertebrate striated muscle and the focal adhesions of nonmuscle cells in their anchorage to the plasma membrane and their major proteins ( Figure 2F and Figure 3A and 3B). [15][16][17] Over the past 7 years, it has been reported that multiple protein complexes link the muscle cell membrane to thick filaments at the M-line in C elegans ( Figure 3A). The cytoplasmic tail of integrin is associated with a complex of 4 conserved proteins [UNC-112 (Kindlin in mammals), PAT-4 (integrin linked kinase, ILK), PAT-6 (Actopaxin), and UNC-97 (PINCH)].…”

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Caenorhabditis elegans Muscle

Benian

Epstein²

2011

Circulation Research

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Abstract:The nematode Caenorhabditis elegans has become established as a major experimental organism with applications to many biomedical research areas. The body wall muscle cells are a useful model for the study of human cardiomyocytes and their homologous structures and proteins. The ability to readily identify mutations affecting these proteins and structures in C elegans and to be able to rigorously characterize their genotypes and phenotypes at the cellular and molecular levels permits mechanistic studies of the responsible interactions relevant to the inherited human cardiomyopathies. Future work in C elegans muscle holds great promise in uncovering new mechanisms in the pathogenesis of these cardiac disorders. (Circ Res. 2011;109:1082-1095.) Key Words: cardiomyopathies Ⅲ Caenorhabditis elegans sarcomere structure Ⅲ sarcomere assembly Ⅲ model genetics C ardiomyopathies are a diverse set of heart muscle diseases associated with mechanical and electric dysfunction and high risk of sudden cardiac death and cardiac failure. The 2 major clinical types of inherited cardiomyopathy are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) 1-3 (Figure 1). Clinical histories indicate a positive family history in about 60% of HCM, and in 20% to 35% of DCM cases. The remaining primary HCM or DCM cases are strongly suspected to be unrecognized familial disease or new mutations. The most common inheritance pattern is autosomal dominant, but at a much lower frequency, autosomal recessive and X-linked recessive inheritance patterns are also observed. Over the past 20 years, more than 450 mutations in 20 genes have been discovered as causing HCM. Nearly all of the affected proteins are components of the sarcomere. The genes most commonly affected encode ␤-myosin heavy chain 4,5 and myosin-binding protein C 6,7 (accounting for at least 25% each), and troponin T, troponin I, tropomyosin, and regulatory myosin light chain (accounting for approximately 2-5% each). 2,8 To date, mutations in more than 30 genes result in DCM. Most of these genes also encode sarcomeric proteins. Interestingly, different mutations in the same gene can result in either HCM or DCM. Currently, we only know the causative mutation for 50% of the cases of HCM, and 20% of the cases of DCM. Despite knowing that mutations in so many different sarcomere and sarcomere-associated proteins result in HCM and DCM, the exact molecular mechanisms by which these mutations result in clinical heart hypertrophy or dilatation, are unknown.

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Molecular Structure of Sarcomere-to-Membrane Attachment at M-Lines inC. elegansMuscle

Cited by 33 publications

References 57 publications

High‐resolution imaging of muscle attachment structures in Caenorhabditis elegans

High‐resolution imaging of muscle attachment structures in Caenorhabditis elegans

A Molecular Mechanism for the Requirement of PAT-4 (Integrin-linked Kinase (ILK)) for the Localization of UNC-112 (Kindlin) to Integrin Adhesion Sites

Caenorhabditis elegans Muscle

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