2015 Vol. 6, No. 10

News and views
BMPR2 spruces up the endothelium in pulmonary hypertension
Jianhua Xiong
2015, 6(10): 703-708. doi: 10.1007/s13238-015-0208-7
The journey of nisin development in China, a natural-green food preservative
Jie Zhang, Jin Zhong
2015, 6(10): 709-711. doi: 10.1007/s13238-015-0214-9
Induction of innate immunity and its perturbation by influenza viruses
Mohsan Ullah Goraya, Song Wang, Muhammad Munir, Ji-Long Chen
2015, 6(10): 712-721. doi: 10.1007/s13238-015-0191-z
Influenza A viruses (IAV) are highly contagious pathogens causing dreadful losses to human and animal, around the globe. IAVs first interact with the host through epithelial cells, and the viral RNA containing a 5'-triphosphate group is thought to be the critical trigger for activation of effective innate immunity via pattern recognition receptors-dependent signaling pathways. These induced immune responses establish the antiviral state of the host for effective suppression of viral replication and enhancing viral clearance. However, IAVs have evolved a variety of mechanisms by which they can invade host cells, circumvent the host immune responses, and use the machineries of host cells to synthesize and transport their own components, which help them to establish a successful infection and replication. In this review, we will highlight the molecular mechanisms of how IAV infection stimulates the host innate immune system and strategies by which IAV evades host responses.
Atg7 in development and disease: panacea or Pandora's Box?
Jianhua Xiong
2015, 6(10): 722-734. doi: 10.1007/s13238-015-0195-8
Macroautophagy is an evolutionarily conserved intracellular degradation system used by life ranging from yeasts to mammals. The core autophagic machinery is composed of ATG (autophagy-related) protein constituents. One particular member of the ATG protein family, Atg7, has been the focus of recent research. Atg7 acts as an E1-like activating enzyme facilitating both microtubule-associated protein light chain 3 (LC3)-phosphatidylethanolamine and ATG12 conjugation. Thus, Atg7 stands at the hub of these two ubiquitin-like systems involving LC3 and Atg12 in autophagic vesicle expansion. In this review, I focus on the pleiotropic function of Atg7 in development, maintenance of health, and alternations of such control in disease.
Research articles
Direct intercellular communications dominate the interaction between adipose-derived MSCs and myofibroblasts against cardiac fibrosis
Xiaokang Li, Hui Zhao, Chunxiao Qi, Yang Zeng, Feng Xu, Yanan Du
2015, 6(10): 735-745. doi: 10.1007/s13238-015-0196-7
The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells (MSCs) has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mechanism of MSC therapy for cardiac fibrosis, we investigated the interplay between MSCs and cardiac myofibroblasts (mFBs) using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor (HGF), a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs' anti-fibrosis function. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions.
Enhanced metastasis in RNF13 knockout mice is mediated by a reduction in GM-CSF levels
He Cheng, Aodi Wang, Jiao Meng, Yong Zhang, Dahai Zhu
2015, 6(10): 746-756. doi: 10.1007/s13238-015-0188-7
RING finger protein 13 (RNF13) is a novel E3 ubiquitin ligase whose expression is associated with cancer development. However, its specific role in cancer progression and metastasis remains unclear. Here, a B16F10/LLC experimental pulmonary metastatic model was developed to examine the formation of metastatic foci in the lung. A greater number of tumor colonies were observed in the lungs of RNF13-knockout (KO) mice than in their wild-type (WT) littermates, whereas no significant differences in tumor size were observed between the two groups. In short-term experiments, the number of fluorescently-labeled B16F10 cells increased remarkably in RNF13-KO lungs at early time points, whereas clearance of tumor cells from the blood was not affected. These results indicated that RNF13 may inhibit the colonization of B16F10 cells in the lung. Assessment of the concentration of various cytokines in tumor bearing lungs and blood did not detect significant differences between the blood of RNF13-KO and WT mice; however the levels of GM-CSF were significantly reduced in RNF13-KO tumor bearing lungs, which may have guided more B16F10 cells to migrate to the lungs. This was confirmed by lower GM-CSF concentrations in conditioned media from the culture of RNF13-KO lung slices. Collectively, our results suggest that host RNF13 affects the concentration of GM-CSF in tumor-bearing lungs, leading to a reduction in the colonization of metastatic tumor cells in the lung.
Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen α
Xinyue Zhang, Meng Wu, Wei Zhuo, Jinke Gu, Sensen Zhang, Jingpeng Ge, Maojun Yang
2015, 6(10): 757-766. doi: 10.1007/s13238-015-0205-x
Bone sialoprotein-binding protein (Bbp), a MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family protein expressed on the surface of Staphylococcus aureus (S. aureus), mediates adherence to fibrinogen α (Fg α), a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp273-598 and Bbp273-598-Fg α561-575 complex at a resolution of 2.03 Å and 1.45 Å, respectively. Apo-Bbp273-598 contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional D1 strand in N2 domain and D1' and D2' strands in N3 domain. The peptide mapped to the Fg α561-575 bond to Bbp273-598 on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a β-strand G" covering the ligand upon ligand binding. BbpAla298-Gly301 in the N2 domain of the Bbp273-598-Fg α561-575 complex, which is a loop in the apo-form, formed a short α-helix to interact tightly with the peptide. In addition, BbpSer547-Gln561 in the N3 domain moved toward the binding groove to make contact directly with the peptide, while BbpAsp338-Gly355 and BbpThr365-Tyr387 in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process.
Atypical group 1 neuraminidase pH1N1-N1 bound to a group 1 inhibitor
Ying Wu, Christopher J. Vavricka, Yan Wu, Qing Li, Santosh Rudrawar, Robin J. Thomson, Mark von Itzstein, George F. Gao, Jianxun Qi
2015, 6(10): 771-773. doi: 10.1007/s13238-015-0197-6
Novel binders derived from an albumin-binding domain scaffold targeting human prostate secretory protein 94 (PSP94)
Lucie Marečková, Hana Petroková, Radim Osička, Milan Kuchař, Petr Malý
2015, 6(10): 774-779. doi: 10.1007/s13238-015-0194-9