Endocytic recycling proteins EHD1 and EHD2 interact with Fer-1-like-5 (Fer1L5) and mediate myoblast fusion

Avery D. Posey, Peter Pytel, Konstantina Gardikiotes, Alexis R. Demonbreun, Mark Rainey, Manju George, Hamid Band, Elizabeth M. McNally

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The mammalian ferlins are calcium-sensing, C2 domain-containing proteins involved in vesicle trafficking. Myoferlin and dysferlin regulate myoblast fusion and muscle membrane resealing, respectively. Correspondingly, myoferlin is most highly expressed in singly nucleated myoblasts, whereas dysferlin expression is increased in mature, multinucleated myotubes. Myoferlin also mediates endocytic recycling and participates in trafficking the insulin-like growth factor receptor. We have now characterized a novel member of the ferlin family, Fer1L5, because of its high homology to dysferlin and myoferlin. We found that Fer1L5 protein is expressed in small myotubes that contain only two to four nuclei. We also found that Fer1L5 protein binds directly to the endocytic recycling proteins EHD1 and EHD2 and that the second C2 domain in Fer1L5 mediates this interaction. Reduction of EHD1 and/or EHD2 inhibits myoblast fusion, and EHD2 is required for normal translocation of Fer1L5 to the plasma membrane. The characterization of Fer1L5 and its interaction with EHD1 and EHD2 underscores the complex requirement of ferlin proteins and mediators of endocytic recycling for membrane trafficking events during myotube formation.

Original languageEnglish (US)
Pages (from-to)7379-7388
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number9
DOIs
StatePublished - Mar 4 2011

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Myoblasts
Recycling
Fusion reactions
Skeletal Muscle Fibers
Proteins
Membranes
Somatomedin Receptors
Membrane Fusion
Cell membranes
Muscle
Cell Membrane
Calcium
Muscles
C2 Domains

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Endocytic recycling proteins EHD1 and EHD2 interact with Fer-1-like-5 (Fer1L5) and mediate myoblast fusion. / Posey, Avery D.; Pytel, Peter; Gardikiotes, Konstantina; Demonbreun, Alexis R.; Rainey, Mark; George, Manju; Band, Hamid; McNally, Elizabeth M.

In: Journal of Biological Chemistry, Vol. 286, No. 9, 04.03.2011, p. 7379-7388.

Research output: Contribution to journalArticle

Posey, Avery D. ; Pytel, Peter ; Gardikiotes, Konstantina ; Demonbreun, Alexis R. ; Rainey, Mark ; George, Manju ; Band, Hamid ; McNally, Elizabeth M. / Endocytic recycling proteins EHD1 and EHD2 interact with Fer-1-like-5 (Fer1L5) and mediate myoblast fusion. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 9. pp. 7379-7388.
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