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EHD1 and EHD2 interact with Fer1L5 to mediate myoblast fusion
Author(s) -
Posey Avery,
Pytel Peter,
Heretis Konstantina,
Demonbreun Alexis,
George Manju,
Rainey Mark,
Band Hamid,
McNally Elizabeth M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb145
Subject(s) - endocytic cycle , dysferlin , microbiology and biotechnology , myogenesis , endocytosis , chemistry , myocyte , biology , cell , biochemistry , gene
Myoferlin and dysferlin regulate myoblast fusion and muscle membrane resealing, respectively. Correspondingly, myoferlin is most highly expressed in singly nucleated myoblasts while dysferlin expression is highest in mature, multinucleated myotubes. The mammalian ferlins are calcium‐sensing, C2 domain‐containing proteins involved in vesicle trafficking. Myoferlin mediates endocytic recycling and participates in trafficking the insulin like growth factor receptor. We 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 abundantly expressed in nascent myotubes containing only 2–4 nuclei. We also found that fer1l5 protein binds directly to the endocytic recycling proteins, EHD1 and EHD2, and that this interaction is mediated by the second C2 domain in fer1l5. Loss of EHD1 and/or EHD2 inhibits myoblast fusion, and EHD2 is required for normal translocation of fer1L5 to the plasma membrane. Abolishing the nucleotide binding ability of the EHD2 ATPase domain recapitulates the fer1L5 translocation defect. 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.