Visualizing sarcomere and cellular dynamics in skeletal muscle to improve cell therapies.

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  • Additional Information
    • Source:
      Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
    • Subject Terms:
      Sarcomeres*/metabolism ; Muscle, Skeletal*/metabolism; Animals ; Mice ; Cell- and Tissue-Based Therapy/methods ; Connectin/metabolism ; Connectin/genetics ; Cell Fusion ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Myoblasts/metabolism ; Gene Knock-In Techniques ; Red Fluorescent Protein
    • Abstract:
      The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. The logistics underlying myofilament assembly and disassembly have started to emerge with the possibility to follow labeled sarcomere components. Here, we generated the mCherry knock-in at titin's Z-disk to study skeletal muscle development and remodeling. We find titin's integration into the sarcomere tightly regulated and its unexpected mobility facilitating a homogeneous distribution of titin after cell fusion - an integral part of syncytium formation and maturation of skeletal muscle. In adult mCherry-titin mice, treatment of muscle injury by implantation of titin-eGFP myoblasts reveals how myocytes integrate, fuse, and contribute to the continuous myofilament system across cell boundaries. Unlike in immature primary cells, titin proteins are retained at the proximal nucleus and do not diffuse across the whole syncytium with implications for future cell-based therapies of skeletal muscle disease.
      Competing Interests: JH, FR, MR, CF, DF, SP, MF, EW, SL, MG No competing interests declared
      (© 2024, Hüttemeister et al.)
    • Grant Information:
      ERCAdv International ERC_ European Research Council; CRC1470 + Single Deutsche Forschungsgemeinschaft; MD3-Nanopathology Deutsches Zentrum für Herz-Kreislaufforschung
    • Contributed Indexing:
      Keywords: cell biology; live imaging; medicine; mouse; muscle; proteostasis; regeneration; sarcomere; titin
    • Accession Number:
      0 (Connectin)
      0 (Luminescent Proteins)
      0 (Red Fluorescent Protein)
    • Publication Date:
      Date Created: 20241217 Date Completed: 20241217 Latest Revision: 20241217
    • Publication Date:
      20241217
    • Accession Number:
      10.7554/eLife.95597
    • Accession Number:
      39688479