title: Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity.
abstract: Obscurin is a large myofibrillar protein that contains several interacting modules, one of which mediates binding to muscle-specific ankyrins. Interaction between obscurin and the muscle-specific ankyrin sAnk1.5 regulates the organization of the sarcoplasmic reticulum in striated muscles. Additional muscle-specific ankyrin isoforms, ankB and ankG, are localized at the subsarcolemma level, at which they contribute to the organization of dystrophin and β-dystroglycan at costameres. In this paper, we report that in mice deficient for obscurin, ankB was displaced from its localization at the M band, whereas localization of ankG at the Z disk was not affected. In obscurin KO mice, localization at costameres of dystrophin, but not of β-dystroglycan, was altered, and the subsarcolemma microtubule cytoskeleton was disrupted. In addition, these mutant mice displayed marked sarcolemmal fragility and reduced muscle exercise tolerance. Altogether, the results support a model in which obscurin, by targeting ankB at the M band, contributes to the organization of subsarcolemma microtubules, localization of dystrophin at costameres, and maintenance of sarcolemmal integrity.
authors: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
authors: Davide
authors: D
authors: Randazzo
authors: Emiliana
authors: E
authors: Giacomello
authors: Stefania
authors: S
authors: Lorenzini
authors: Daniela
authors: D
authors: Rossi
authors: Enrico
authors: E
authors: Pierantozzi
authors: Bert
authors: B
authors: Blaauw
authors: Carlo
authors: C
authors: Reggiani
authors: Stephan
authors: S
authors: Lange
authors: Angela K
authors: AK
authors: Peter
authors: Ju
authors: J
authors: Chen
authors: Vincenzo
authors: V
authors: Sorrentino
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D054974:Costameres / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D049030:Dystroglycans / Q000378:metabolism; D016189:Dystrophin / Q000032:analysis / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport; D064067:Rho Guanine Nucleotide Exchange Factors; D012508:Sarcolemma / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C498995:Ank2 protein, mouse; C094681:Ank3 protein, mouse; D017487:Ankyrins; D016189:Dystrophin; D020662:Guanine Nucleotide Exchange Factors; D009124:Muscle Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D049030:Dystroglycans; D017346:Protein Serine-Threonine Kinases; C515766:obscn protein, mouse