Plectin 1 links intermediate filaments to costameric sarcolemma through beta-synemin, alpha-dystrobrevin and actin.
In skeletal muscles, the sarcolemma is possibly stabilized and protected against contraction-imposed stress by intermediate filaments (IFs) tethered to costameric sarcolemma. Although there is emerging evidence that plectin links IFs to costameres through dystrophin-glycoprotein complexes (DGC), the molecular organization from plectin to costameres still remains unclear. Here, we show that plectin 1, a plectin isoform expressed in skeletal muscle, can interact with beta-synemin, actin and a DGC component, alpha-dystrobrevin, in vitro. Ultrastructurally, beta-synemin molecules appear to be incorporated into costameric dense plaques, where they seem to serve as actin-associated proteins rather than IF proteins. In fact, they can bind actin and alpha-dystrobrevin in vitro. Moreover, in vivo immunoprecipitation analyses demonstrated that beta-synemin- and plectin-immune complexes from lysates of muscle light microsomes contained alpha-dystrobrevin, dystrophin, nonmuscle actin, metavinculin, plectin and beta-synemin. These findings suggest a model in which plectin 1 interacts with DGC and integrin complexes directly, or indirectly through nonmuscle actin and beta-synemin within costameres. The DGC and integrin complexes would cooperate to stabilize and fortify the sarcolemma by linking the basement membrane to IFs through plectin 1, beta-synemin and actin. Besides, the two complexes, together with plectin and IFs, might have their own functions as platforms for distinct signal transduction.
Hijikata
Takao
T
Department of Anatomy and Cell Biology, Faculty of Pharmacy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan. hijikata@musashino-u.ac.jp
Nakamura
Akio
A
Isokawa
Keitaro
K
Imamura
Michihiro
M
Yuasa
Katsutoshi
K
Ishikawa
Ryoki
R
Kohama
Kazuhiro
K
Takeda
Shinichi
S
Yorifuji
Hiroshi
H
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016189:Dystrophin / Q000172:deficiency / Q000378:metabolism; D049029:Dystrophin-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D007382:Intermediate Filaments / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism; D051190:Plectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism / Q000648:ultrastructure
D000199:Actins; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D007381:Intermediate Filament Proteins; D050505:Mutant Proteins; D051190:Plectin; C098885:dystrobrevin; C491443:synemin protein, mouse