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Regulatory Function of Sympathetic Innervation on the Endo/Lysosomal Trafficking of Acetylcholine Receptor

Straka, Tatjana; Schröder, Charlotte; Roos, Andreas; Kollipara, Laxmikanth; Sickmann, Albert; Williams, Marion Patrick Ivey; Hafner, Mathias; Khan, Muzamil Majid; Rudolf, Rüdiger

Recent studies have demonstrated that neuromuscular junctions are co-innervated by sympathetic neurons. This co-innervation has been shown to be crucial for neuromuscular junction morphology and functional maintenance. To improve our understanding of how sympathetic innervation affects nerve–muscle synapse homeostasis, we here used in vivo imaging, proteomic, biochemical, and microscopic approaches to compare normal and sympathectomized mouse hindlimb muscles. Live confocal microscopy revealed reduced fiber diameters, enhanced acetylcholine receptor turnover, and increased amounts of endo/lysosomal acetylcholine-receptor-bearing vesicles. Proteomics analysis of sympathectomized skeletal muscles showed that besides massive changes in mitochondrial, sarcomeric, and ribosomal proteins, the relative abundance of vesicular trafficking markers was affected by sympathectomy. Immunofluorescence and Western blot approaches corroborated these findings and, in addition, suggested local upregulation and enrichment of endo/lysosomal progression and autophagy markers, Rab 7 and p62, at the sarcomeric regions of muscle fibers and neuromuscular junctions. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000131144
Veröffentlicht am 12.04.2021
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 1664-042X
KITopen-ID: 1000131144
Erschienen in Frontiers in Physiology
Verlag Frontiers Media
Band 12
Seiten Art.-Nr.: 626707
Nachgewiesen in Scopus
Web of Science
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