Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy

Kee, Anthony J.; Schevzov, Galina; Nair-Shalliker, Visalini; Robinson, Charles Alexander; Vrhovski, Bernadette; Ghoddusi, Majid; Qiu, Min; Lin, Jim Jung‐Ching; Weinberger, Ron P.; Gunning, Peter W.; Hardeman, Edna C.

doi:10.1083/jcb.200406181

Cited by 55 publications

(77 citation statements)

References 68 publications

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“…Recently, Tm antibodies have also been used to identify a novel non-muscle cytoskeletal compartment in muscle cells that might be involved in the pathology of muscular dystrophy (Kee et al 2004). In addition, Tm5a/Tm5b have been shown to mark an apical population of microfilaments that can regulate the insertion and/or retention of an apical chloride channel, CFTR (cystic fibrosis transmembrane conductance regulator) (Dalby-Payne et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific Tropomyosin Isoform Composition

Schevzov¹,

Vrhovski²,

Bryce³

et al. 2005

J Histochem Cytochem.

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106

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S U M M A R Y Four distinct genes encode tropomyosin (Tm) proteins, integral components of the actin microfilament system. In non-muscle cells, over 40 Tm isoforms are derived using alternative splicing. Distinct populations of actin filaments characterized by the composition of these Tm isoforms are found differentially sorted within cells (Gunning et al. 1998b). We hypothesized that these distinct intracellular compartments defined by the association of Tm isoforms may allow for independent regulation of microfilament function. Consequently, to understand the molecular mechanisms that give rise to these different microfilaments and their regulation, a cohort of fully characterized isoform-specific Tm antibodies was required. The characterization protocol initially involved testing the specificity of the antibodies on bacterially produced Tm proteins. We then confirmed that these Tm antibodies can be used to probe the expression and subcellular localization of different Tm isoforms by Western blot analysis, immunofluorescence staining of cells in culture, and immunohistochemistry of paraffin wax-embedded mouse tissues. These Tm antibodies, therefore, have the capacity to monitor specific actin filament populations in a range of experimental systems.

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Section: Discussionmentioning

confidence: 99%

Tissue-specific Tropomyosin Isoform Composition

Schevzov¹,

Vrhovski²,

Bryce³

et al. 2005

J Histochem Cytochem.

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106

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“…3A, mXin␣ was coimmunoprecipitated from gastrocnemius muscle extracts using anti-tropomyosin (LC24), antifilamin, anti-vinculin, or anti-talin mAb but not anti-␤-catenin mAb or normal mouse serum control. mAb LC24 recognizes tropomyosin isoform 4 that is known to locate together with ␥-actin external to the sarcomere but adjacent to the Z-line and in the subsarcolemmal region including MTJ in skeletal muscle cells (28,58). The antibodies used in our experiments specifically precipitated their respective antigens from skeletal muscle extract except for anti-␤-catenin (Fig.…”

Section: Similar But Distinguishable Localizations For Mxin␣ and Mxinmentioning

confidence: 99%

Localization and function of Xinα in mouse skeletal muscle

Feng

Wang

Reiter

et al. 2013

American Journal of Physiology-Cell Physiology

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The Xin repeat-containing proteins were originally found in the intercalated discs of cardiac muscle with implicated roles in cardiac development and function. A pair of paralogous genes, Xin␣ (Xirp1) and Xin␤ (Xirp2), is present in mammals. Ablation of the mouse Xin␣ (mXin␣) did not affect heart development but caused late-onset adulthood cardiac hypertrophy and cardiomyopathy with conductive defects. Both mXin␣ and mXin␤ are also found in the myotendinous junction (MTJ) of skeletal muscle. Here we investigated the structural and functional significance of mXin␣ in skeletal muscle. In addition to MTJ and the contact sites between muscle and perimysium, mXin␣ but not mXin␤ was found in the blood vessel walls, whereas both proteins were absent in neuromuscular junctions and nerve fascicles. Coimmunoprecipitation suggested association of mXin␣ with talin, vinculin, and filamin, but not ␤-catenin, in adult skeletal muscle, consistent with our previous report of colocalization of mXin␣ with vinculin. Loss of mXin␣ in mXin␣-null mice had subtle effects on the MTJ structure and the levels of several MTJ components. Diaphragm muscle of mXin␣-null mice showed hypertrophy. Compared with wild-type controls, mouse extensor digitorum longus (EDL) muscle lacking mXin␣ exhibited no overt change in contractile and relaxation velocities or maximum force development but better tolerance to fatigue. Loaded fatigue contractions generated stretch injury in wild-type EDL muscle as indicated by a fragmentation of troponin T. This effect was blunted in mXin␣-null EDL muscle. The results suggest that mXin␣ play a role in MTJ conductance of contractile and stretching forces.

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“…Using the existing nonspecific antibodies with ␣/2a may help shed light on isoform distribution and whether any switching occurs during development, analogous to that seen in brain development (Weinberger et al 1996;Schevzov et al 1997;Hannan et al 1998). Indeed, there is a growing body of evidence to suggest that many different cell types sort tropomyosin isoforms into spatially segregated actin populations in brain (Gunning et al 1998a,b), fibroblasts (Percival et al 2000(Percival et al ,2004, epithelial cells (Dalby-Payne et al 2003), and skeletal muscle (Kee et al 2004).…”

Section: Tropomyosin In the Lungmentioning

confidence: 99%

Smooth Muscle-specific α Tropomyosin Is a Marker of Fully Differentiated Smooth Muscle in Lung

Vrhovski

McKay

Schevzov

et al. 2005

J Histochem Cytochem.

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S U M M A R Y Tropomyosin (Tm) is one of the major components of smooth muscle. Currently it is impossible to easily distinguish the two major smooth muscle (sm) forms of Tm at a protein level by immunohistochemistry due to lack of specific antibodies. ␣ -sm Tm contains a unique 2a exon not found in any other Tm. We have produced a polyclonal antibody to this exon that specifically detects ␣ -sm Tm. We demonstrate here the utility of this antibody for the study of smooth muscle. The tissue distribution of ␣ -sm Tm was shown to be highly specific to smooth muscle. ␣ -sm Tm showed an identical profile and tissue colocalization with ␣ -sm actin both by Western blotting and immunohistochemistry. Using lung as a model organ system, we examined the developmental appearance of ␣ -sm Tm in comparison to ␣ -sm actin in both the mouse and human. ␣ -sm Tm is a late-onset protein, appearing much later than actin in both species. There were some differences in onset of appearance in vascular and airway smooth muscle with airway appearing earlier. ␣ -sm Tm can therefore be used as a good marker of mature differentiated smooth muscle cells. Along with ␣ -sm actin and sm-myosin antibodies, ␣ -sm Tm is a valuable tool for the study of smooth muscle.

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Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy

Cited by 55 publications

References 68 publications

Tissue-specific Tropomyosin Isoform Composition

Tissue-specific Tropomyosin Isoform Composition

Localization and function of Xinα in mouse skeletal muscle

Smooth Muscle-specific α Tropomyosin Is a Marker of Fully Differentiated Smooth Muscle in Lung

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