title: A thioredoxin fold protein Sh3bgr regulates Enah and is necessary for proper sarcomere formation.
abstract: The sh3bgr (SH3 domain binding glutamate-rich) gene encodes a small protein containing a thioredoxin-like fold, SH3 binding domain, and glutamate-rich domain. Originally, it was suggested that increased expression of Sh3bgr may cause the cardiac phenotypes in Down's syndrome. However, it was recently reported that the overexpression of Sh3bgr did not cause any disease phenotypes in mice. In this study, we have discovered that Sh3bgr is critical for sarcomere formation in striated muscle tissues and also for heart development. Sh3bgr is strongly expressed in the developing somites and heart in Xenopus. Morpholino mediated-knockdown of sh3bgr caused severe malformation of heart tissue and disrupted segmentation of the somites. Further analysis revealed that Sh3bgr specifically localized to the Z-line in mature sarcomeres and that knockdown of Sh3bgr completely disrupted sarcomere formation in the somites. Moreover, overexpression of Sh3bgr resulted in abnormally discontinues thick firmaments in the somitic sarcomeres. We suggest that Sh3bgr does its function at least partly by regulating localization of Enah for the sarcomere formation. In addition, we provide the data supporting Sh3bgr is also necessary for proper heart development in part by affecting the Enah protein level.
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Korea.
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: Jang
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Sim
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Song
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Sofia
authors.initials: S
authors.lastname: Medina-Ruiz
authors.affiliation: UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, Korea.
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Seo
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Korea. Electronic address: parktj@unist.ac.kr.
authors.forename: Tae Joo
authors.initials: TJ
authors.lastname: Park
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism*; D024510:Muscle Development; D054792:Muscle, Striated / Q000196:embryology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D017433:Protein Structure, Secondary; D021381:Protein Transport; D012518:Sarcomeres / Q000378:metabolism*; D019170:Somites / Q000196:embryology / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C000602339:Enah protein, Xenopus; D008840:Microfilament Proteins; C000602338:Sh3bgr protein, Xenopus; D029867:Xenopus Proteins; D013879:Thioredoxins