title: Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with beta-dystroglycan.
abstract: In skeletal muscle, the cytolinker plectin is prominently expressed at Z-disks and the sarcolemma. Alternative splicing of plectin transcripts gives rise to more than eight protein isoforms differing only in small N-terminal sequences (5-180 residues), four of which (plectins 1, 1b, 1d, and 1f) are found at substantial levels in muscle tissue. Using plectin isoform-specific antibodies and isoform expression constructs, we show the differential regulation of plectin isoforms during myotube differentiation and their localization to different compartments of muscle fibers, identifying plectins 1 and 1f as sarcolemma-associated isoforms, whereas plectin 1d localizes exclusively to Z-disks. Coimmunoprecipitation and in vitro binding assays using recombinant protein fragments revealed the direct binding of plectin to dystrophin (utrophin) and beta-dystroglycan, the key components of the dystrophin-glycoprotein complex. We propose a model in which plectin acts as a universal mediator of desmin intermediate filament anchorage at the sarcolemma and Z-disks. It also explains the plectin phenotype observed in dystrophic skeletal muscle of mdx mice and Duchenne muscular dystrophy patients.
authors: Max F. Perutz Laboratories, Department of Molecular Cell Biology, University of Vienna, A-1030 Vienna, Austria.
authors: Günther A
authors: GA
authors: Rezniczek
authors: Patryk
authors: P
authors: Konieczny
authors: Branislav
authors: B
authors: Nikolic
authors: Siegfried
authors: S
authors: Reipert
authors: Doris
authors: D
authors: Schneller
authors: Christina
authors: C
authors: Abrahamsberg
authors: Kay E
authors: KE
authors: Davies
authors: Steve J
authors: SJ
authors: Winder
authors: Gerhard
authors: G
authors: Wiche
mesh_terms: D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D003893:Desmin / Q000378:metabolism; D049030:Dystroglycans / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051190:Plectin / Q000276:immunology / Q000378:metabolism*; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D049411:Utrophin / Q000378:metabolism
chemical_list: D003893:Desmin; C495333:Plec protein, mouse; D051190:Plectin; D020033:Protein Isoforms; D049411:Utrophin; D049030:Dystroglycans