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(American Journal of Pathology. 1999;154:591-600.)
© 1999 American Society for Investigative Pathology

Regular Articles

Specific and Innervation-Regulated Expression of the Intermediate Filament Protein Nestin at Neuromuscular and Myotendinous Junctions in Skeletal Muscle

Samuli Vaittinen* , Riitta Lukka* , Cecilia Sahlgren , Jussi Rantanen , Timo Hurme§ , Urban Lendahl¶ , John E. Eriksson|| and Hannu Kalimo*

From the Departments of Pathology,* Surgery, and Pediatric Surgery,§ Turku University Hospital, the Department of Biology, Åbo Akademi University, and the Turku Centre for Biotechnology,^|| University of Turku and Åbo Akademi University, Turku, Finland; and the Department of Cell and Molecular Biology,^¶ Karolinska Institute, Stockholm, and the Division of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Huddinge, Sweden

The intermediate filament proteins nestin, vimentin, and desmin show a specific temporal expression pattern during the development of myofibers from myogenic 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 maintaining structural integrity. In this study we have analyzed the expression levels and distribution pattern of nestin in intact and denervated muscle in rat and in human. Nestin immunoreactivity was specifically and focally localized in the sarcoplasm underneath neuromuscular junctions (NMJs) and in the vicinity of the myotendinous junctions (MTJs), ie, in regions associated with acetylcholine receptors (AChRs). This association prompted us to analyze nestin in neurogenically and myogenically denervated muscle. Immunoblot analysis disclosed a marked overall increase of accumulated nestin protein. Similar to the extrajunctional redistribution of AChRs in denervated myofibers, nestin immunoreactivity extended widely beyond the NMJ region. Re-innervation caused complete reversion of these changes. Our study demonstrates that the expression levels and distribution pattern of nestin are regulated by innervation, ie, signal transduction into myofibers.

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