title: Endocytic recycling proteins EHD1 and EHD2 interact with fer-1-like-5 (Fer1L5) and mediate myoblast fusion.
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.
authors.affiliation: Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Avery D
authors.initials: AD
authors.lastname: Posey
authors.forename: Peter
authors.initials: P
authors.lastname: Pytel
authors.forename: Konstantina
authors.initials: K
authors.lastname: Gardikiotes
authors.forename: Alexis R
authors.initials: AR
authors.lastname: Demonbreun
authors.forename: Mark
authors.initials: M
authors.lastname: Rainey
authors.forename: Manju
authors.initials: M
authors.lastname: George
authors.forename: Hamid
authors.initials: H
authors.lastname: Band
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: McNally
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000073939:Dysferlin; D011992:Endosomes / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering; D012508:Sarcolemma / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C497505:Dysf protein, mouse; D000073939:Dysferlin; C485117:EHD2 protein, mouse; C485640:Ehd1 protein, mouse; C557795:FER1L5 protein, mouse; D008565:Membrane Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; C521810:myoferlin protein, mouse