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

J Biol Chem. 2008 Jul 18;283(29):20252-60. doi: 10.1074/jbc.M802306200. Epub 2008 May 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium-Binding Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Fusion
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Conserved Sequence
  • Endocytosis*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Myoblasts / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Transferrin / metabolism

Substances

  • Calcium-Binding Proteins
  • Carrier Proteins
  • EHD2 protein, mouse
  • MYOF protein, human
  • Membrane Proteins
  • Muscle Proteins
  • Transferrin
  • myoferlin protein, mouse