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Dysferlin-mediated phosphatidylserine sorting engages macrophages in sarcolemma repair

Author

Listed:
  • Volker Middel

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT))

  • Lu Zhou

    (Institute of Applied Physics, Karlsruhe Institute of Technology (KIT)
    Institute of Nanotechnology, Karlsruhe Institute of Technology (KIT))

  • Masanari Takamiya

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT))

  • Tanja Beil

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT))

  • Maryam Shahid

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT))

  • Urmas Roostalu

    (Institute of Inflammation and Repair, The University of Manchester)

  • Clemens Grabher

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT))

  • Sepand Rastegar

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT))

  • Markus Reischl

    (Institute for Applied Computer Science, Karlsruhe Institute of Technology (KIT))

  • Gerd Ulrich Nienhaus

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT)
    Institute of Applied Physics, Karlsruhe Institute of Technology (KIT)
    Institute of Nanotechnology, Karlsruhe Institute of Technology (KIT)
    University of Illinois at Urbana-Champaign)

  • Uwe Strähle

    (Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT))

Abstract

Failure to repair the sarcolemma leads to muscle cell death, depletion of stem cells and myopathy. Hence, membrane lesions are instantly sealed by a repair patch consisting of lipids and proteins. It has remained elusive how this patch is removed to restore cell membrane integrity. Here we examine sarcolemmal repair in live zebrafish embryos by real-time imaging. Macrophages remove the patch. Phosphatidylserine (PS), an ‘eat-me’ signal for macrophages, is rapidly sorted from adjacent sarcolemma to the repair patch in a Dysferlin (Dysf) dependent process in zebrafish and human cells. A previously unrecognized arginine-rich motif in Dysf is crucial for PS accumulation. It carries mutations in patients presenting with limb-girdle muscular dystrophy 2B. This underscores the relevance of this sequence and uncovers a novel pathophysiological mechanism underlying this class of myopathies. Our data show that membrane repair is a multi-tiered process involving immediate, cell-intrinsic mechanisms as well as myofiber/macrophage interactions.

Suggested Citation

  • Volker Middel & Lu Zhou & Masanari Takamiya & Tanja Beil & Maryam Shahid & Urmas Roostalu & Clemens Grabher & Sepand Rastegar & Markus Reischl & Gerd Ulrich Nienhaus & Uwe Strähle, 2016. "Dysferlin-mediated phosphatidylserine sorting engages macrophages in sarcolemma repair," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12875
    DOI: 10.1038/ncomms12875
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