Muscle activity and muscle agrin regulate the organization of cytoskeletal proteins and attached acetylcholine receptor (AchR) aggregates in skeletal muscle fibers.
In innervated skeletal muscle fibers, dystrophin and beta-dystroglycan form rib-like structures (costameres) that appear as predominantly transverse stripes over Z and M lines. Here, we show that the orientation of these stripes becomes longitudinal in denervated muscles and transverse again in denervated electrically stimulated muscles. Skeletal muscle fibers express nonneural (muscle) agrin whose function is not well understood. In this work, a single application of > or = 10 nM purified recombinant muscle agrin into denervated muscles preserved the transverse orientation of costameric proteins that is typical for innervated muscles, as did a single application of > or = 1 microM neural agrin. At lower concentration, neural agrin induced acetylcholine receptor aggregates, which colocalized with longitudinally oriented beta-dystroglycan, dystrophin, utrophin, syntrophin, rapsyn, and beta 2-laminin in denervated unstimulated fibers and with the same but transversely oriented proteins in innervated or denervated stimulated fibers. The results indicate that costameres are plastic structures whose organization depends on electrical muscle activity and/or muscle agrin.
Bezakova
G
G
Department of Physiology, University of Oslo, 0317 Oslo, Norway. gabriela.bizakova@unibas.ch
Lømo
T
T
D018171:Agrin / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D049030:Dystroglycans; D016189:Dystrophin / Q000378:metabolism; D049029:Dystrophin-Associated Proteins; D004558:Electric Stimulation; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D020033:Protein Isoforms / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011940:Receptor Aggregation / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D049411:Utrophin
D018171:Agrin; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D007797:Laminin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; D049411:Utrophin; C051609:peripheral membrane protein 43K; C091824:syntrophin; C058783:laminin beta2; D049030:Dystroglycans