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Dysferlin-mediated phosphatidylserine sorting engages macrophages in sarcolemma repair

Middel, Volker; Zhou, Lu; Takamiya, Masanari; Beil, Tanja; Shahid, Maryam; Roostalu, Urmas; Grabher, Clemens; Rastegar, Sepand; Reischl, Markus; Nienhaus, Gerd Ulrich; Strähle, Uwe

Abstract (englisch): 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.

Zugehörige Institution(en) am KIT Institut für Angewandte Physik (APH)
Institut für Angewandte Informatik (IAI)
Institut für Nanotechnologie (INT)
Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Jahr 2016
Sprache Englisch
Identifikator DOI: 10.1038/ncomms12875
ISSN: 2041-1723
URN: urn:nbn:de:swb:90-594637
KITopen ID: 1000059463
HGF-Programm 47.01.01; LK 01
Erschienen in Nature Communications
Band 7
Seiten 12875
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
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