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EMBO Reports

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https://www.readbyqxmd.com/read/28420656/posttranslational-modification-impact-on-the-mechanism-by-which-amyloid-%C3%AE-induces-synaptic-dysfunction
#1
Katarzyna M Grochowska, PingAn Yuanxiang, Julia Bär, Rajeev Raman, Gemma Brugal, Giriraj Sahu, Michaela Schweizer, Arthur Bikbaev, Stephan Schilling, Hans-Ulrich Demuth, Michael R Kreutz
Oligomeric amyloid-β (Aβ) 1-42 disrupts synaptic function at an early stage of Alzheimer's disease (AD). Multiple posttranslational modifications of Aβ have been identified, among which N-terminally truncated forms are the most abundant. It is not clear, however, whether modified species can induce synaptic dysfunction on their own and how altered biochemical properties can contribute to the synaptotoxic mechanisms. Here, we show that a prominent isoform, pyroglutamated Aβ3(pE)-42, induces synaptic dysfunction to a similar extent like Aβ1-42 but by clearly different mechanisms...
April 18, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28404606/local-translation-in-neuronal-compartments-how-local-is-local
#2
REVIEW
Vidhya Rangaraju, Susanne Tom Dieck, Erin M Schuman
Efficient neuronal function depends on the continued modulation of the local neuronal proteome. Local protein synthesis plays a central role in tuning the neuronal proteome at specific neuronal regions. Various aspects of translation such as the localization of translational machinery, spatial spread of the newly translated proteins, and their site of action are carried out in specialized neuronal subcompartments to result in a localized functional outcome. In this review, we focus on the various aspects of these local translation compartments such as size, biochemical and organelle composition, structural boundaries, and temporal dynamics...
April 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28396575/the-role-of-biology-in-global-climate-change-interdisciplinary-research-in-biogeochemistry-can-help-to-understand-local-and-global-fluxes-of-carbon-and-other-elements-and-inform-environmental-policies
#3
https://www.readbyqxmd.com/read/28396574/healthy-children-without-fear-reproductive-options-for-patients-or-couples-carrying-inherited-diseases
#4
Joep Geraedts
No abstract text is available yet for this article.
April 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28396573/synapses-in-the-spotlight-with-synthetic%C3%A2-optogenetics
#5
REVIEW
Shai Berlin, Ehud Y Isacoff
Membrane receptors and ion channels respond to various stimuli and relay that information across the plasma membrane by triggering specific and timed processes. These include activation of second messengers, allowing ion permeation, and changing cellular excitability, to name a few. Gaining control over equivalent processes is essential to understand neuronal physiology and pathophysiology. Recently, new optical techniques have emerged proffering new remote means to control various functions of defined neuronal populations by light, dubbed optogenetics...
April 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28396572/vesicular-stomatitis-virus-n-protein-specific-single-domain-antibody-fragments-inhibit-replication
#6
Leo Hanke, Florian I Schmidt, Kevin E Knockenhauer, Benjamin Morin, Sean Pj Whelan, Thomas U Schwartz, Hidde L Ploegh
The transcription and replication machinery of negative-stranded RNA viruses presents a possible target for interference in the viral life cycle. We demonstrate the validity of this concept through the use of cytosolically expressed single-domain antibody fragments (VHHs) that protect cells from a lytic infection with vesicular stomatitis virus (VSV) by targeting the viral nucleoprotein N. We define the binding sites for two such VHHs, 1004 and 1307, by X-ray crystallography to better understand their inhibitory properties...
April 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28389464/chromatin-determinants-impart-camptothecin-sensitivity
#7
Fabio Puddu, Israel Salguero, Mareike Herzog, Nicola J Geisler, Vincenzo Costanzo, Stephen P Jackson
Camptothecin-induced locking of topoisomerase 1 on DNA generates a physical barrier to replication fork progression and creates topological stress. By allowing replisome rotation, absence of the Tof1/Csm3 complex promotes the conversion of impending topological stress to DNA catenation and causes camptothecin hypersensitivity. Through synthetic viability screening, we discovered that histone H4 K16 deacetylation drives the sensitivity of yeast cells to camptothecin and that inactivation of this pathway by mutating H4 K16 or the genes SIR1-4 suppresses much of the hypersensitivity of tof1∆ strains towards this agent...
April 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28381482/usp26-regulates-tgf-%C3%AE-signaling-by-deubiquitinating-and-stabilizing-smad7
#8
Sarah Kit Leng Lui, Prasanna Vasudevan Iyengar, Patrick Jaynes, Zul Fazreen Bin Adam Isa, Brendan Pang, Tuan Zea Tan, Pieter Johan Adam Eichhorn
The amplitude of transforming growth factor-β (TGF-β) signal is tightly regulated to ensure appropriate physiological responses. As part of negative feedback loop SMAD7, a direct transcriptional target of downstream TGF-β signaling acts as a scaffold to recruit the E3 ligase SMURF2 to target the TGF-β receptor complex for ubiquitin-mediated degradation. Here, we identify the deubiquitinating enzyme USP26 as a novel integral component of this negative feedback loop. We demonstrate that TGF-β rapidly enhances the expression of USP26 and reinforces SMAD7 stability by limiting the ubiquitin-mediated turnover of SMAD7...
April 5, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28381481/fkbp8-recruits-lc3a-to-mediate-parkin-independent-mitophagy
#9
Zambarlal Bhujabal, Åsa B Birgisdottir, Eva Sjøttem, Hanne B Brenne, Aud Øvervatn, Sabrina Habisov, Vladimir Kirkin, Trond Lamark, Terje Johansen
Mitophagy, the selective removal of damaged or excess mitochondria by autophagy, is an important process in cellular homeostasis. The outer mitochondrial membrane (OMM) proteins NIX, BNIP3, FUNDC1, and Bcl2-L13 recruit ATG8 proteins (LC3/GABARAP) to mitochondria during mitophagy. FKBP8 (also known as FKBP38), a unique member of the FK506-binding protein (FKBP) family, is similarly anchored in the OMM and acts as a multifunctional adaptor with anti-apoptotic activity. In a yeast two-hybrid screen, we identified FKBP8 as an ATG8-interacting protein...
April 5, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28377371/molecular-basis-for-cdk1-regulated-timing-of-mis18-complex-assembly-and-cenp-a-deposition
#10
Frances Spiller, Bethan Medina-Pritchard, Maria Alba Abad, Martin A Wear, Oscar Molina, William C Earnshaw, A Arockia Jeyaprakash
The centromere, a chromosomal locus that acts as a microtubule attachment site, is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during the cell cycle requires HJURP-mediated CENP-A deposition, a process regulated by the Mis18 complex (Mis18α/Mis18β/Mis18BP1). Spatial and temporal regulation of Mis18 complex assembly is crucial for its centromere association and function. Here, we provide the molecular basis for the assembly and regulation of the Mis18 complex. We show that the N-terminal region of Mis18BP1 spanning amino acid residues 20-130 directly interacts with Mis18α/β to form the Mis18 complex...
April 4, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28364023/rna-activation-independent-dna-targeting-of-the-type-iii-crispr-cas-system-by-a-csm-complex
#11
Kwang-Hyun Park, Yan An, Tae-Yang Jung, In-Young Baek, Haemin Noh, Woo-Chan Ahn, Hans Hebert, Ji-Joon Song, Jeong-Hoon Kim, Byung-Ha Oh, Eui-Jeon Woo
The CRISPR-Cas system is an adaptive and heritable immune response that destroys invading foreign nucleic acids. The effector complex of the Type III CRISPR-Cas system targets RNA and DNA in a transcription-coupled manner, but the exact mechanism of DNA targeting by this complex remains elusive. In this study, an effector Csm holocomplex derived from Thermococcus onnurineus is reconstituted with a minimalistic combination of Csm1121334151, and shows RNA targeting and RNA-activated single-stranded DNA (ssDNA) targeting activities...
March 31, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28364022/the-phosphorylation-status-of-t522-modulates-tissue-specific-functions-of-sirt1-in-energy-metabolism-in-mice
#12
Jing Lu, Qing Xu, Ming Ji, Xiumei Guo, Xiaojiang Xu, David C Fargo, Xiaoling Li
SIRT1, the most conserved mammalian NAD(+)-dependent protein deacetylase, is an important metabolic regulator. However, the mechanisms by which SIRT1 is regulated in vivo remain unclear. Here, we report that phosphorylation modification of T522 on SIRT1 is crucial for tissue-specific regulation of SIRT1 activity in mice. Dephosphorylation of T522 is critical for repression of its activity during adipogenesis. The phospho-T522 level is reduced during adipogenesis. Knocking-in a constitutive T522 phosphorylation mimic activates the β-catenin/GATA3 pathway, repressing PPARγ signaling, impairing differentiation of white adipocytes, and ameliorating high-fat diet-induced dyslipidemia in mice...
March 31, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28356328/technology-versus-biology-the-limits-of-pre-implantation-genetic-screening-better-methods-to-detect-the-origin-of-aneuploidy-in-pre-implantation-embryos-could-improve-the-success-rate-of-artificial-reproduction
#13
https://www.readbyqxmd.com/read/28348000/the-impact-of-environment-on-abnormal-behavior-and-mental-disease-to-alleviate-the-prevalence-of-mental-disorders-we-need-to-phenotype-the-environment-for-risk-factors
#14
https://www.readbyqxmd.com/read/28341812/parkinson-s-disease-associated-receptor-gpr37-is-an-er-chaperone-for-lrp6
#15
Birgit S Berger, Sergio P Acebron, Jessica Herbst, Stefan Koch, Christof Niehrs
Wnt/β-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky β-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/β-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis...
March 24, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28336777/switching-genes-to-silent-mode-near-dna-double-strand-breaks
#16
Sophie E Polo
No abstract text is available yet for this article.
March 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28336776/apoptosis-inhibitor-5-is-an-endogenous-inhibitor-of-caspase-2
#17
Gergely Imre, Jean Berthelet, Jan Heering, Sebastian Kehrloesser, Inga Maria Melzer, Byung Il Lee, Bernd Thiede, Volker Dötsch, Krishnaraj Rajalingam
Caspases are key enzymes responsible for mediating apoptotic cell death. Across species, caspase-2 is the most conserved caspase and stands out due to unique features. Apart from cell death, caspase-2 also regulates autophagy, genomic stability and ageing. Caspase-2 requires dimerization for its activation which is primarily accomplished by recruitment to high molecular weight protein complexes in cells. Here, we demonstrate that apoptosis inhibitor 5 (API5/AAC11) is an endogenous and direct inhibitor of caspase-2...
March 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28336775/nelf-e-is-recruited-to-dna-double-strand-break-sites-to-promote-transcriptional-repression-and-repair
#18
Samah W Awwad, Enas R Abu-Zhayia, Noga Guttmann-Raviv, Nabieh Ayoub
Double-strand breaks (DSBs) trigger rapid and transient transcription pause to prevent collisions between repair and transcription machineries at damage sites. Little is known about the mechanisms that ensure transcriptional block after DNA damage. Here, we reveal a novel role of the negative elongation factor NELF in blocking transcription activity nearby DSBs. We show that NELF-E and NELF-A are rapidly recruited to DSB sites. Furthermore, NELF-E recruitment and its repressive activity are both required for switching off transcription at DSBs...
March 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28336774/in-situ-structure-of-the-legionella-dot-icm-type-iv-secretion-system-by-electron-cryotomography
#19
Debnath Ghosal, Yi-Wei Chang, Kwangcheol C Jeong, Joseph P Vogel, Grant J Jensen
Type IV secretion systems (T4SSs) are large macromolecular machines that translocate protein and DNA and are involved in the pathogenesis of multiple human diseases. Here, using electron cryotomography (ECT), we report the in situ structure of the Dot/Icm type IVB secretion system (T4BSS) utilized by the human pathogen Legionella pneumophila This is the first structure of a type IVB secretion system, and also the first structure of any T4SS in situ While the Dot/Icm system shares almost no sequence similarity with type IVA secretion systems (T4ASSs), its overall structure is seen here to be remarkably similar to previously reported T4ASS structures (those encoded by the R388 plasmid in Escherichia coli and the cag pathogenicity island in Helicobacter pylori)...
March 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28330855/conserved-atg8-recognition-sites-mediate-atg4-association-with-autophagosomal-membranes-and-atg8-deconjugation
#20
Susana Abreu, Franziska Kriegenburg, Rubén Gómez-Sánchez, Muriel Mari, Jana Sánchez-Wandelmer, Mads Skytte Rasmussen, Rodrigo Soares Guimarães, Bettina Zens, Martina Schuschnig, Ralph Hardenberg, Matthias Peter, Terje Johansen, Claudine Kraft, Sascha Martens, Fulvio Reggiori
Deconjugation of the Atg8/LC3 protein family members from phosphatidylethanolamine (PE) by Atg4 proteases is essential for autophagy progression, but how this event is regulated remains to be understood. Here, we show that yeast Atg4 is recruited onto autophagosomal membranes by direct binding to Atg8 via two evolutionarily conserved Atg8 recognition sites, a classical LC3-interacting region (LIR) at the C-terminus of the protein and a novel motif at the N-terminus. Although both sites are important for Atg4-Atg8 interaction in vivo, only the new N-terminal motif, close to the catalytic center, plays a key role in Atg4 recruitment to autophagosomal membranes and specific Atg8 deconjugation...
March 22, 2017: EMBO Reports
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