Specific and innervation-regulated expression of the intermediate filamentprotein nestin at neuromuscular and myotendinous junctions in skeletal muscle

The intermediate filament proteins nestin, vimentin, and desmin show a spec ific temporal expression pattern during the development of myofibers from m yogenic precursor cells. Nestin and vimentin are actively expressed during early developmental stages to be later down-regulated, vimentin completely and nestin to minimal levels, whereas desmin expression begins later and is maintained in mature myofibers, in which desmin participates in maintainin g structural integrity. In this study we have analyzed the expression level s and distribution pattern of nestin in intact and denervated muscle in rat and in human. Nestin immunoreactivity was specifically and focally localiz ed in the sarcoplasm underneath neuromuscular junctions (NMJs) and in the v icinity of the myotendinous junctions (MTJs), ie, in regions associated wit h acetylcholine receptors (AChRs). This association prompted us to analyze nestin in neurogenically and myogenically denervated muscle. Immunoblot ana lysis disclosed a marked overall increase of accumulated nestin protein. Si milar to the extrajunctional redistribution of AChRs in denervated myofiber s, nestin immunoreactivity extended widely beyond the NMJ region. Re-innerv ation caused complete reversion of these changes. Our study demonstrates th at the expression levels and distribution pattern of nestin are regulated b y innervation, ie, signal transduction into myofibers.