2013 Vol. 4(7)

Dr. Zhen-Yi Wang: Fighting leukemia
Ming Li, Guang-Biao Zhou
2013, 4(7): 483-484. doi: 10.1007/s13238-013-3802-6
UV-B-induced photomorphogenesis in Arabidopsis
Jigang Li, Li Yang, Dan Jin, Cynthia D. Nezames, William Terzaghi, Xing Wang Deng
2013, 4(7): 485-492. doi: 10.1007/s13238-013-3036-7
Ultraviolet-B (UV-B) is a relatively minor component of sunlight, but can induce stress-related physiological processes or UV-B-specific photomorphogenic responses in plants. In the last decade, significant progress has been made in understanding the UV-B photomorphogenic pathway, including identification of the key components in the pathway, molecular characterization of UV-B photoreceptor and perception mechanism, and elucidation of the signal transduction mechanisms from the photoactivated UV-B receptor to downstream gene expression. This review summarizes the key players identified to date in the UV-B photomorphogenic pathway and their roles in mediating UV-B signal transduction.
Co-evolution of plant LTR-retrotransposons and their host genomes
Meixia Zhao, Jianxin Ma
2013, 4(7): 493-501. doi: 10.1007/s13238-013-3037-6
Transposable elements (TEs), particularly, long terminal repeat retrotransposons (LTR-RTs), are the most abundant DNA components in all plant species that have been investigated, and are largely responsible for plant genome size variation. Although plant genomes have experienced periodic proliferation and/or recent burst of LTRretrotransposons, the majority of LTR-RTs are inactivated by DNA methylation and small RNA-mediated silencing mechanisms, and/or were deleted/truncated by unequal homologous recombination and illegitimate recombination, as suppression mechanisms that counteract genome expansion caused by LTR-RT amplification. LTR-RT DNA is generally enriched in pericentromeric regions of the host genomes, which appears to be the outcomes of preferential insertions of LTR-RTs in these regions and low effectiveness of selection that purges LTR-RT DNA from these regions relative to chromosomal arms. Potential functions of various TEs in their host genomes remain blurry; nevertheless, LTR-RTs have been recognized to play important roles in maintaining chromatin structures and centromere functions and regulation of gene expressions in their host genomes.
Research articles
Structure and receptor-binding properties of an airborne transmissible avian influenza A virus hemagglutinin H5 (VN1203mut)
Xishan Lu, Yi Shi, Wei Zhang, Yanfang Zhang, Jianxun Qi, George F Gao
2013, 4(7): 502-511. doi: 10.1007/s13238-013-3906-z
Avian influenza A virus continues to pose a global threat with occasional H5N1 human infections, which is emphasized by a recent severe human infection caused by avian-origin H7N9 in China. Luckily these viruses do not transmit efficiently in human populations. With a few amino acid substitutions of the hemagglutinin H5 protein in the laboratory, two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model. Here in this study one of the mutant H5 proteins developed by Kawaoka's group (VN1203mut) was expressed in a baculovirus system and its receptor-binding properties were assessed. We herein show that the VN1203mut had a dramatically reduced binding affinity for the avian α2,3-linkage receptor compared to wild type but showed no detectable increase in affinity for the human α2,6-linkage receptor, using Surface Plasmon Resonance techonology. Further, the crystal structures of the VN1203mut and its complexes with either human or avian receptors demonstrate that the VN1203mut binds the human receptor in the same binding manner (cis conformation) as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses. Our receptor binding and crystallographic data shown here further confirm that the ability to bind the avian receptor has to decrease for a higher human receptor binding affinity. As the Q226L substitution is shown important for obtaining human receptor binding, we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.
The differential requirement of mushroom body α/β subdivisions in long-term memory retrieval in Drosophila
Cheng Huang, Pengzhi Wang, Zhiyong Xie, Lianzhang Wang, Yi Zhong
2013, 4(7): 512-519. doi: 10.1007/s13238-013-3035-8
The mushroom body (MB), a bilateral brain structure possessing about 2000-2500 neurons per hemisphere, plays a central role in olfactory learning and memory in Drosophila melanogaster. Extensive studies have demonstrated that three major types of MB neurons (α/β, α'/β' and γ) exhibit distinct functions in memory processing, including the critical role of approximately 1000 MB α/β neurons in retrieving long-term memory. Inspired by recent findings that MB α/β neurons can be further divided into three subdivisions (surface, posterior and core) and wherein the α/β core neurons play an permissive role in long-term memory consolidation, we examined the functional differences of all the three morphological subdivisions of MB α/β by temporally precise manipulation of their synaptic outputs during long-term memory retrieval. We found the normal neurotransmission from a combination of MB α/β surface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory, whereas output from MB α/β posterior or core subdivision alone is dispensable. These results imply a specific requirement of about 500 MB α/β neurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MB α/β region.
Angiotensin IV upregulates the activity of protein phosphatase 1α in Neura-2A cells
Dan Wang, Peng Xue, Xiu Lan Chen, Zhen Sheng Xie, Fu Quan Yang, Li Zheng, Tao Xu
2013, 4(7): 520-528. doi: 10.1007/s13238-013-3005-1
The peptide angiotensin IV (Ang IV) is a derivative of angiotensin Ⅱ. While insulin regulated amino peptidase (IRAP) has been proposed as a potential receptor for Ang IV, the signalling pathways of Ang IV through IRAP remain elusive. We applied high-resolution mass spectrometry to perform a systemic quantitative phosphoproteome of Neura-2A (N2A) cells treated with and without Ang IV using stable-isotope labeling by amino acids in cell culture (SILAC), and identified a reduction in the phosphorylation of a major Ser/Thr protein phosphorylase 1 (PP1) upon Ang IV treatment. In addition, spinophilin (spn), a PP1 regulatory protein that plays important functions in the neural system, was expressed at higher levels. Immunoblotting revealed decreased phosphorylation of p70S6 kinase (p70S6K) and the major cell cycle modulator retinoblastoma protein (pRB). These changes are consistent with an observed decrease in cell proliferation. Taken together, our study suggests that Ang IV functions via regulating the activity of PP1.
Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome
Hua Li, Shuxian Wu, Liming Mao, Guowei Lei, Liping Zhang, Ailing Lu, Liguo An, Guiwen Yang, Paride Abliz, Guangxun Meng
2013, 4(7): 529-538. doi: 10.1007/s13238-013-2127-9
The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical arms of host innate immunity, which is a protein complex controlling maturation of IL-1β. To clarify whether T. schoenleinii is able to activate the inflammasome, we analyzed human monocytic cell line THP-1 for IL-1β production upon infection with T. schoenleinii strain isolated from Tinea favosa patients, and rapid IL-1β secretion from THP-1 cells was observed. Moreover, applying competitive inhibitors and gene specific silencing with shRNA, we found that T. schoenleinii induced IL-1β secretion, ASC pyroptosome formation as well as caspase-1 activation were all dependent on NLRP3. Cathepsin B activity, ROS production and K+ efflux were required for the inflammasome activation by T. schoenleinii. Our data thus reveal that the NLRP3 inflammasome plays an important role in host defense against T. schoenleinii, and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T. schoenleinii infection.
Chrysin promotes osteogenic differentiation via ERK/MAPK activation
Wenfeng Zeng, Yan Yan, Fayun Zhang, Chunling Zhang, Wei Liang
2013, 4(7): 539-547. doi: 10.1007/s13238-013-3003-3
The effect of the anti-inflammatory flavonoid chrysin on osteogenesis was determined in preosteoblast MC3T3-E1 cells. Results demonstrated that chrysin could induce osteogenic differentiation in the absence of other osteogenic agents. Chrysin treatment promoted the expression of transcription factors (Runx2 and Osx) and bone formation marker genes (Col1A1, OCN, and OPN) as well as enhanced the formation of mineralized nodules. During osteogenic differentiation, chrysin preferentially activated ERK1/2, but not JNK nor the p38 MAPKs. Further experiments with inhibitors revealed the co-treatment of U0126, PD98059, or ICI182780 (a general ER antagonist) with chrysin effectively abrogated the chrysin-induced osteogenesis and ERK1/2 activation. Thus, the effect of chrysin on osteogenesis is ERK1/2-dependent and involves ER. Therefore, chrysin has the significant potential to enhance osteogenesis for osteoporosis prevention and treatment.
Crystal structures and biochemical studies of human lysophosphatidic acid phosphatase type 6
Jun Li, Yu Dong, Xingru Lü, Lu Wang, Wei Peng, Xuejun C. Zhang, Zihe Rao
2013, 4(7): 548-561. doi: 10.1007/s13238-013-3031-z
Lysophosphatidic acid (LPA) is an important bioactive phospholipid involved in cell signaling through Gprotein-coupled receptors pathways. It is also involved in balancing the lipid composition inside the cell, and modulates the function of lipid rafts as an intermediate in phospholipid metabolism. Because of its involvement in these important processes, LPA degradation needs to be regulated as precisely as its production. Lysophosphatidic acid phosphatase type 6 (ACP6) is an LPA-specific acid phosphatase that hydrolyzes LPA to monoacylglycerol (MAG) and phosphate. Here, we report three crystal structures of human ACP6 in complex with malonate, L-(+)-tartrate and tris, respectively. Our analyses revealed that ACP6 possesses a highly conserved Rossmann-foldlike body domain as well as a less conserved cap domain. The vast hydrophobic substrate-binding pocket, which is located between those two domains, is suitable for accommodating LPA, and its shape is different from that of other histidine acid phosphatases, a fact that is consistent with the observed difference in substrate preferences. Our analysis of the binding of three molecules in the active site reveals the involvement of six conserved and crucial residues in binding of the LPA phosphate group and its catalysis. The structure also indicates a water-supplying channel for substrate hydrolysis. Our structural data are consistent with the fact that the enzyme is active as a monomer. In combination with additional mutagenesis and enzyme activity studies, our structural data provide important insights into substrate recognition and the mechanism for catalytic activity of ACP6.

Current Issue

March, 2019

Volume 10, Issue 3

Pages 157-233

About the cover

Metastasis is the leading cause of human cancer deaths.Unfortunately, no approved drugs are available for antimetastatic treatment. In this study, high-throughputsequencing-based high-throughput screening (HTS2) anda breast cancer lung metastasis (BCLM)-associated genesignature were combined to discover anti-metastatic drugs.After screening of thousands of compounds, Shao et al.identifed Ponatinib as a BCLM inhibitor. Ponatinib signifcantlyinhibited the migration and mammosphere formation of breastcancer cells in vitro and blocked BCLM in multiple mousemodels. This study may facilitate the therapeutic treatment ofBCLM as well as other metastases.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang Beijing 100101, China

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