title: ClipR-59 interacts with Elmo2 and modulates myoblast fusion.
abstract: Recent studies using ClipR-59 knock-out mice implicated this protein in the regulation of muscle function. In this report, we have examined the role of ClipR-59 in muscle differentiation and found that ClipR-59 knockdown in C2C12 cells suppressed myoblast fusion. To elucidate the molecular mechanism whereby ClipR-59 regulates myoblast fusion, we carried out a yeast two-hybrid screen using ClipR-59 as the bait and identified Elmo2, a member of the Engulfment and cell motility protein family, as a novel ClipR-59-associated protein. We showed that the interaction between ClipR-59 and Elmo2 was mediated by the atypical PH domain of Elmo2 and the Glu-Pro-rich domain of ClipR-59 and regulated by Rho-GTPase. We have examined the impact of ClipR-59 on Elmo2 downstream signaling and found that interaction of ClipR-59 with Elmo2 enhanced Rac1 activation. Collectively, our studies demonstrate that formation of an Elmo2·ClipR-59 complex plays an important role in myoblast fusion.
authors.affiliation: From the State Key Laboratory for Agro-biotechnology, College of Biological Science, China Agricultural University, 10083 Beijing, China, the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, and.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, and.
authors.forename: Wenying
authors.initials: W
authors.lastname: Ren
authors.affiliation: the Institut de Recherches Cliniques de Montréal, Montréal, Université de Montréal, Québec H2W 1R7, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Côté
authors.affiliation: the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, and.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Hinds
authors.affiliation: From the State Key Laboratory for Agro-biotechnology, College of Biological Science, China Agricultural University, 10083 Beijing, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, and kdu@tuftsmedicalcenter.org.
authors.forename: Keyong
authors.initials: K
authors.lastname: Du
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics; D024510:Muscle Development / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C539981:ClipR-59 protein, mouse; D003598:Cytoskeletal Proteins; C544335:Elmo2 protein, mouse; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein
keywords: Differentiation; Dock1; Muscle; Myogenesis; Protein-protein Interaction; Rho (Rho GTPase)