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.

Single-Cell Resolution of Temporal Gene Expression during Heart Development

“…“Perfect marker” gene analyses of PCA-separated CMs identified eight sarcomere protein genes ( Table S3 , bolded) and Sh3bgr , which encodes a SH3 domain binding glutamate-rich protein encoded within the trisomy chromosome 21 region that contributes to congenital heart defects. Morpholino-mediated knockdown of Sh3bgr in Xenopus, results in disrupted segmentation of somites and heart malformations (Jang et al, 2015). Eight “perfect marker” genes for ECs encoded prototypic molecules (Pecam1, Cdh5) and two additional genes: Klhl4 and Gpr116 ( Table S3 , italicized).…”

Construction of LncRNA-Related ceRNA Networks in Longissimus Dorsi Muscle of Jinfen White Pigs at Different Developmental Stages

“…ENAH, a member of this class of proteins, is involved in somite development [50], and ENAH has been discovered to be a target of miR-127 in this study. A study showed that Sh3bgr regulates skeletal muscle development by cooperating with ENAH [51]. Here, the expression trends of Sh3bgr and ENAH were parallel and showed an increase with age, also indicating that these factors may interact to participate in skeletal muscle development.…”

Single-Cell Analysis Uncovers Osteoblast Factor Growth Differentiation Factor 10 as Mediator of Vascular Smooth Muscle Cell Phenotypic Modulation Associated with Plaque Rupture in Human Carotid Artery Disease

“…Interestingly, the gene expression profile recapitulates different aspects of VSMC phenotypic switch, such as VSMC proliferation, migration, lipid accumulation, calcification, adipogenesis and osteogenic development (Dpep1 [32], Scara5 [33,34], Smoc2 [35], Clec11a, Dpt [36,37]) (Supplementary Figure S3b). In contrast, the genes upregulated in the DT aorta of Apoe −/− mice on an NCD exhibited an atheroprotective gene expression profile linked to cardiac and skeletal muscle development, vasodilation, cholesterol efflux and VSMC phenotype preservation (Ptprz1 [38,39], Ramp1 [40], Hdac9n [41], Sh3bgr [42,43]) (Supplementary Figure S3b). The vascular sitespecific transcription signature reveals molecular determinants of atherosclerotic disease susceptibility or protection even before the onset of hypercholesteremia-induced atherogenic stress.…”