2015 Vol. 6, No. 11

The creation of synthetic crystalline bovine insulin
Yeping Sun
2015, 6(11): 781-783. doi: 10.1007/s13238-015-0221-x
Vantage points
How does transmembrane electrochemical potential drive the rotation of Fo motor in an ATP synthase?
Xuejun C. Zhang, Min Liu, Yan Zhao
2015, 6(11): 784-791. doi: 10.1007/s13238-015-0217-6
New discovery rarely runs smooth: an update on progranulin/TNFR interactions
Betty C. Wang, Helen Liu, Ankoor Talwar, Jinlong Jian
2015, 6(11): 792-803. doi: 10.1007/s13238-015-0213-x
Progranulin (PGRN) is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors (TNFR) and has therapeutic effects in inflammatory arthritis (Tang et. al, in Science 332:478-484, 2011); however, Chen et al. reported their inability to demonstrate the PGRN-TNFR interactions under their own conditions (Chen et. al, in J Neurosci 33:9202-9213, 2013). A letter-to-editor was then published by the original group in response to the Chen et al. paper that discussed the reasons for the latter's inability to recapitulate the interactions. In addition, the group published follow-up studies that further reinforced and dissected the interactions of PGRNTNFR. Recently, the dispute about the legitimacy of PGRN-TNFR interactions appears to be finally settled with independent confirmations of these interactions in various conditions by numerous laboratories. This review presents a chronological update on the story of PGRN-TNFR interactions, highlighting the independent confirmations of these interactions in various diseases and conditions.
Role of transcription factor acetylation in the regulation of metabolic homeostasis
Joo-Man Park, Seong-Ho Jo, Mi-Young Kim, Tae-Hyun Kim, Yong-Ho Ahn
2015, 6(11): 804-813. doi: 10.1007/s13238-015-0204-y
Post-translational modifications (PTMs) of transcription factors play a crucial role in regulating metabolic homeostasis. These modifications include phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, and O-GlcNAcylation. Recent studies have shed light on the importance of lysine acetylation at nonhistone proteins including transcription factors. Acetylation of transcription factors affects subcellular distribution, DNA affinity, stability, transcriptional activity, and current investigations are aiming to further expand our understanding of the role of lysine acetylation of transcription factors. In this review, we summarize recent studies that provide new insights into the role of protein lysine-acetylation in the transcriptional regulation of metabolic homeostasis.
Research articles
TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope
Shuai Yuan, Lei Cao, Hui Ling, Minghao Dang, Yao Sun, Xuyuan Zhang, Yutao Chen, Liguo Zhang, Dan Su, Xiangxi Wang, Zihe Rao
2015, 6(11): 814-824. doi: 10.1007/s13238-015-0220-y
Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons underlying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.
Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells
Xin Chen, Weiwei Ma, Tingxin Zhang, Longyan Wu, Hai Qi
2015, 6(11): 825-832. doi: 10.1007/s13238-015-0210-0
How follicular T-helper (Tfh) cells develop is incompletely understood. We find that, upon antigen exposure in vivo, both naïve and antigen-experienced T cells sequentially upregulate CXCR5 and Bcl6 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6+CXCR5+ Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6hiCXCR5hi phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.
Apaf1 inhibition promotes cell recovery from apoptosis
Anna Gortat, Mónica Sancho, Laura Mondragón, Àngel Messeguer, Enrique Pérez-Payá, Mar Orzáez
2015, 6(11): 833-843. doi: 10.1007/s13238-015-0200-2
The protein apoptotic protease activating factor 1 (Apaf1) is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apaf1, cells recover from doxorubicin-or hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apaf1 not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.
Mitochondrial haplogroup B increases the risk for hearing loss among the Eastern Asian pedigrees carrying 12S rRNA 1555A>G mutation
Zhengbiao Ying, Jing Zheng, Zhaoyang Cai, Li Liu, Yu Dai, Juan Yao, Hui Wang, Yinglong Gao, Binjiao Zheng, Xiaowen Tang, Yi Zhu, Min-Xin Guan, Ye Chen
2015, 6(11): 844-848. doi: 10.1007/s13238-015-0203-z
Molecular mechanism for the substrate recognition of USP7
Jingdong Cheng, Ze Li, Rui Gong, Jian Fang, Yi Yang, Chang Sun, Huirong Yang, Yanhui Xu
2015, 6(11): 849-852. doi: 10.1007/s13238-015-0192-y
Drug screening: zebrafish as a tool for studying epileptic-related chemical compounds
Sha-Sha Zhao, Yi-Liao Wang, Ming-Zhu Sun, Lu Lu, Ya-Nan Wang, Delaney Pfister, Jessica Lee, Xin Zhao, Xi-Zeng Feng, Lei Li
2015, 6(11): 853-857. doi: 10.1007/s13238-015-0206-9