title: In vivo imaging of molecular interactions at damaged sarcolemma.
abstract: Muscle cells have a remarkable capability to repair plasma membrane lesions. Mutations in dysferlin (dysf) are known to elicit a progressive myopathy in humans, probably due to impaired sarcolemmal repair. We show here that loss of Dysf and annexin A6 (Anxa6) function lead to myopathy in zebrafish. By use of high-resolution imaging of myofibers in intact animals, we reveal sequential phases in sarcolemmal repair. Initially, membrane vesicles enriched in Dysf together with cytoplasmic Anxa6 form a tight patch at the lesion independently of one another. In the subsequent steps, annexin A2a (Anxa2a) followed by annexin A1a (Anxa1a) accumulate at the patch; the recruitment of these annexins depends on Dysf and Anxa6. Thus, sarcolemmal repair relies on the ordered assembly of a protein-membrane scaffold. Moreover, we provide several lines of evidence that the membrane for sarcolemmal repair is derived from a specialized plasma membrane compartment.
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology and University of Heidelberg, Eggenstein-Leopoldshafen, Germany. urmas@roostalu.info
authors.forename: Urmas
authors.initials: U
authors.lastname: Roostalu
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017302:Annexins / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D004195:Disease Models, Animal; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics / Q000503:physiopathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000503:physiopathology*; D012508:Sarcolemma / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D015027:Zebrafish / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D017302:Annexins; D008565:Membrane Proteins; D029961:Zebrafish Proteins; C568333:dysf protein, zebrafish