The endocytic recycling protein EHD2 interacts with myoferlin to regulate myoblast fusion

Katherine R. Doherty, Alexis R. Demonbreun, Gregory Q. Wallace, Andrew Cave, Avery D. Posey, Konstantina Heretis, Peter Pytel, Elizabeth M. McNally

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Skeletal muscle is a multinucleated syncytium that develops and is maintained by the fusion of myoblasts to the syncytium. Myoblast fusion involves the regulated coalescence of two apposed membranes. Myoferlin is a membrane-anchored, multiple C2 domain-containing protein that is highly expressed in fusing myoblasts and required for efficient myoblast fusion to myotubes. We found that myoferlin binds directly to the eps15 homology domain protein, EHD2. Members of the EHD family have been previously implicated in endocytosis as well as endocytic recycling, a process where membrane proteins internalized by endocytosis are returned to the plasma membrane. EHD2 binds directly to the second C2 domain of myoferlin, and EHD2 is reduced in myoferlin null myoblasts. In contrast to normal myoblasts, myoferlin null myoblasts accumulate labeled transferrin and have delayed recycling. Introduction of dominant negative EHD2 into myoblasts leads to the sequestration of myoferlin and inhibition of myoblast fusion. The interaction of myoferlin with EHD2 identifies molecular overlap between the endocytic recycling pathway and the machinery that regulates myoblast membrane fusion.

Original languageEnglish (US)
Pages (from-to)20252-20260
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number29
DOIs
StatePublished - Jul 18 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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