Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity

Randazzo, Davide; Giacomello, Emiliana; Lorenzini, Stefania; Rossi, Daniela; Pierantozzi, Enrico; Blaauw, Bert; Reggiani, Carlo; Lange, Stephan; Peter, Angela K.; Chen, Ju; Sorrentino, Vincenzo

doi:10.1083/jcb.201205118

Cited by 62 publications

(56 citation statements)

References 62 publications

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“…At costameres, ankyrin-B complexes with dynactin-4 and β 2 -spectrin, both of which are necessary for the proper localization of dystrophin, a key cytoskeletal protein (Ayalon et al 2008(Ayalon et al , 2011. In the absence of giant obscurins, ankyrin-B is absent from costameres, which results in mislocalized dystrophin and alterations in the organization of costamere-associated microtubules (Randazzo et al 2013). Obscurin knockout mice injected with Evans Blue Dye (EBD) prior to exercise exhibited an increased number of EBD-positive muscle fibers, indicative of muscle fibers with increased muscle damage, similar to the mdx mouse model of muscular dystrophy (Randazzo et al 2013).…”

Section: Obscurins At Costameresmentioning

confidence: 99%

“…The necessity of obscurins for the integration of myosin into A-bands of sarcomeres can be demonstrated by several in vitro studies (Borisov et al , 2006KontrogianniKonstantopoulos et al 2004KontrogianniKonstantopoulos et al , 2006Randazzo et al 2013). Overexpression of the COOH-terminal region of obscurin in developing primary skeletal myotubes dramatically reduces A-band myosin organization, but other proteins of M-bands a n d Z -d i s c s r e m a i n u n c h a n g e d ( K o n t r o g i a n n i - ).…”

Section: Obscurins At the M-band Mediate The Assembly Of Thick Filamentsmentioning

confidence: 99%

“…Obscurin polypeptides interact with ankyrin-B to provide a molecular bridge between membrane and cytoskeletal proteins, thereby promoting the assembly of essential protein complexes in skeletal muscle (Randazzo et al 2013). At costameres, ankyrin-B complexes with dynactin-4 and β 2 -spectrin, both of which are necessary for the proper localization of dystrophin, a key cytoskeletal protein (Ayalon et al 2008(Ayalon et al , 2011.…”

Section: Obscurins At Costameresmentioning

confidence: 99%

“…In the absence of giant obscurins, ankyrin-B is absent from costameres, which results in mislocalized dystrophin and alterations in the organization of costamere-associated microtubules (Randazzo et al 2013). Obscurin knockout mice injected with Evans Blue Dye (EBD) prior to exercise exhibited an increased number of EBD-positive muscle fibers, indicative of muscle fibers with increased muscle damage, similar to the mdx mouse model of muscular dystrophy (Randazzo et al 2013). Therefore, the interaction of obscurin and ankyrin-B is necessary for the proper assembly of the dystrophin complex at costameres and is necessary to maintain sarcolemma integrity in skeletal muscle.…”

Section: Obscurins At Costameresmentioning

confidence: 99%

“…In C. elegans at the M-band, UNC-89 interacts with copine domain protein atypical-1 (CPNA-1), UNC-15 (paramyosin), small CTD-phosphatase-like-1 (SCPL-1), four and a half LIM domains protein 9 (LIM9/FHL), maternal effect lethal 26 (MEL-26), and Rho1 (Gieseler et al 2016;Qadota et al 2008a, b;Warner et al 2013;Wilson et al 2012) and Drosophila obscurins interact with Ball and multiple ankyrin repeats single KH domain (MASK) at the M-band (Katzemich et al 2015). In addition, mammalian obscurins interact with the NH 2 -terminus of titin and Ran-binding protein 9 (RanBP9) at Z-discs (Bowman et al 2008), small ankyrin-1 at the SR , and ankyrin-B at costameres (Randazzo et al 2013). At the ID of mammalian cardiac muscle, obscurin polypeptides interact with N-cadherin and Na + /K + ATPase (Hu and KontrogianniKonstantopoulos 2013).…”

Section: Varied Ligands Of Obscurinsmentioning

confidence: 99%

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Obscure functions: the location–function relationship of obscurins

2017

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The obscurin family of polypeptides is essential for normal striated muscle function and contributes to the pathogenesis of fatal diseases, including cardiomyopathies and cancers. The single mammalian obscurin gene, OBSCN, gives rise to giant (∼800 kDa) and smaller (∼40-500 kDa) proteins that are composed of tandem adhesion and signaling motifs. Mammalian obscurin proteins are expressed in a variety of cell types, including striated muscles, and localize to distinct subcellular compartments where they contribute to diverse cellular processes. Obscurin homologs in Caenorhabditis elegans and Drosophila possess a similar domain architecture and are also expressed in striated muscles. The long sought after question, "what does obscurin do?" is complex and cannot be addressed without taking into consideration the subcellular distribution of these proteins and local isoform concentration. Herein, we present an overview of the functions of obscurins and begin to define the intricate relationship between their subcellular distributions and functions in striated muscles.

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Section: Obscurins At Costameresmentioning

confidence: 99%

Section: Obscurins At the M-band Mediate The Assembly Of Thick Filamentsmentioning

confidence: 99%

Section: Obscurins At Costameresmentioning

confidence: 99%

Section: Obscurins At Costameresmentioning

confidence: 99%

Section: Varied Ligands Of Obscurinsmentioning

confidence: 99%

See 3 more Smart Citations

Obscure functions: the location–function relationship of obscurins

2017

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Myofilaments: Movers and Rulers of the Sarcomere

Lin

Song

Sadayappan

2017

Comprehensive Physiology

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Striated cardiac and skeletal muscles play very different roles in the body, but they are similar at the molecular level. In particular, contraction, regardless of the type of muscle, is a precise and complex process involving the integral protein myofilaments and their associated regulatory components. The smallest functional unit of muscle contraction is the sarcomere. Within the sarcomere can be found a sophisticated ensemble of proteins associated with the thick filaments (myosin, myosin binding protein-C, titin, and obscurin) and thin myofilaments (actin, troponin, tropomyosin, nebulin, and nebulette). These parallel thick and thin filaments slide across one another, pulling the two ends of the sarcomere together to regulate contraction. More specifically, the regulation of both timing and force of contraction is accomplished through an intricate network of intra- and interfilament interactions belonging to each myofilament. This review introduces the sarcomere proteins involved in striated muscle contraction and places greater emphasis on the more recently identified and less well-characterized myofilaments: cardiac myosin binding protein-C, titin, nebulin, and obscurin. © 2017 American Physiological Society. Compr Physiol 7:675-692, 2017.

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Thick Filament Protein Network, Functions, and Disease Association

Wang

Geist

Grogan

et al. 2018

Comprehensive Physiology

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Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that makes up the backbone of the thick filament, four other proteins which are intimately bound to the thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural and regulatory roles. Consistent with this, mutations in the respective genes have been associated with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to summarize our current knowledge on the molecular structure, subcellular localization, interacting partners, function, modulation via posttranslational modifications, and disease involvement of these five major proteins that comprise the thick filament of striated muscle cells. © 2018 American Physiological Society. Compr Physiol 8:631-709, 2018.

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Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity

Abstract: Obscurin contributes to the organization of subsarcolemma microtubules, localization of dystrophin at costameres, and maintenance of sarcolemmal integrity in skeletal muscle fibers.

Cited by 62 publications

References 62 publications

Obscure functions: the location–function relationship of obscurins

Obscure functions: the location–function relationship of obscurins

Myofilaments: Movers and Rulers of the Sarcomere

Thick Filament Protein Network, Functions, and Disease Association

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