title: Interaction of α-catulin with dystrobrevin contributes to integrity of dystrophin complex in muscle.
abstract: The dystrophin complex is a multimolecular membrane-associated protein complex whose defects underlie many forms of muscular dystrophy. The dystrophin complex is postulated to function as a structural element that stabilizes the cell membrane by linking the contractile apparatus to the extracellular matrix. A better understanding of how this complex is organized and localized will improve our knowledge of the pathogenic mechanisms of diseases that involve the dystrophin complex. In a Caenorhabditis elegans genetic study, we demonstrate that CTN-1/α-catulin, a cytoskeletal protein, physically interacts with DYB-1/α-dystrobrevin (a component of the dystrophin complex) and that this interaction is critical for the localization of the dystrophin complex near dense bodies, structures analogous to mammalian costameres. We further show that in mouse α-catulin is localized at the sarcolemma and neuromuscular junctions and interacts with α-dystrobrevin and that the level of α-catulin is reduced in α-dystrobrevin-deficient mouse muscle. Intriguingly, in the skeletal muscle of mdx mice lacking dystrophin, we discover that the expression of α-catulin is increased, suggesting a compensatory role of α-catulin in dystrophic muscle. Together, our study demonstrates that the interaction between α-catulin and α-dystrobrevin is evolutionarily conserved in C. elegans and mammalian muscles and strongly suggests that this interaction contributes to the integrity of the dystrophin complex.
authors.affiliation: Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA.
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Oh
authors.forename: Linu S
authors.initials: LS
authors.lastname: Abraham
authors.forename: Jolanda
authors.initials: J
authors.lastname: van Hengel
authors.forename: Christophe
authors.initials: C
authors.lastname: Stove
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Proszynski
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
authors.forename: Joseph X
authors.initials: JX
authors.lastname: DiMario
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
authors.forename: Frans
authors.initials: F
authors.lastname: van Roy
authors.forename: Hongkyun
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D002853:Chromatography, Liquid / Q000379:methods; D003599:Cytoskeleton / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D053719:Tandem Mass Spectrometry / Q000379:methods; D013696:Temperature; D020798:Two-Hybrid System Techniques; D051178:alpha Catenin / Q000378:metabolism*
chemical_list: D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D020033:Protein Isoforms; D051178:alpha Catenin; C098885:dystrobrevin