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EMBO Reports

Jean-François De Backer, Stéphanie Monlezun, Bérangère Detraux, Adeline Gazan, Laura Vanopdenbosch, Julian Cheron, Giuseppe Cannazza, Sébastien Valverde, Lídia Cantacorps, Mérie Nassar, Laurent Venance, Olga Valverde, Philippe Faure, Michele Zoli, Olivier De Backer, David Gall, Serge N Schiffmann, Alban de Kerchove d'Exaerde
Melanoma antigen genes (Mage) were first described as tumour markers. However, some of Mage are also expressed in healthy cells where their functions remain poorly understood. Here, we describe an unexpected role for one of these genes, Maged1, in the control of behaviours related to drug addiction. Mice lacking Maged1 are insensitive to the behavioural effects of cocaine as assessed by locomotor sensitization, conditioned place preference (CPP) and drug self-administration. Electrophysiological experiments in brain slices and conditional knockout mice demonstrate that Maged1 is critical for cortico-accumbal neurotransmission...
July 12, 2018: EMBO Reports
Arvid Herrmann, Pantelis Livanos, Elisabeth Lipka, Astrid Gadeyne, Marie-Theres Hauser, Daniël Van Damme, Sabine Müller
Kinesins are versatile nano-machines that utilize variable non-motor domains to tune specific motor microtubule encounters. During plant cytokinesis, the kinesin-12 orthologs, PHRAGMOPLAST ORIENTING KINESIN (POK)1 and POK2, are essential for rapid centrifugal expansion of the cytokinetic apparatus, the phragmoplast, toward a pre-selected cell plate fusion site at the cell cortex. Here, we report on the spatio-temporal localization pattern of POK2, mediated by distinct protein domains. Functional dissection of POK2 domains revealed the association of POK2 with the site of the future cell division plane and with the phragmoplast during cytokinesis...
July 12, 2018: EMBO Reports
John D Loike, Alan Kadish
No abstract text is available yet for this article.
July 10, 2018: EMBO Reports
Ana Martínez-Riaño, Elena R Bovolenta, Pilar Mendoza, Clara L Oeste, María Jesús Martín-Bermejo, Paola Bovolenta, Martin Turner, Nuria Martínez-Martín, Balbino Alarcón
Successful vaccines rely on activating a functional humoral response that results from promoting a proper germinal center (GC) reaction. Key in this process is the activation of follicular B cells that need to acquire antigens and to present them to cognate CD4 T cells. Here, we report that follicular B cells can phagocytose large antigen-coated particles, a process thought to be exclusive of specialized antigen-presenting cells such as macrophages and dendritic cells. We show that antigen phagocytosis by B cells is BCR-driven and mechanistically dependent on the GTPase RhoG...
July 9, 2018: EMBO Reports
Justin Kale, Ozgur Kutuk, Glauber Costa Brito, Tallulah S Andrews, Brian Leber, Anthony Letai, David W Andrews
Akt is a pro-survival kinase frequently activated in human cancers and is associated with more aggressive tumors that resist therapy. Here, we connect Akt pathway activation to reduced sensitivity to chemotherapy via Akt phosphorylation of Bax at residue S184, one of the pro-apoptotic Bcl-2 family proteins required for cells to undergo apoptosis. We show that phosphorylation by Akt converts the pro-apoptotic protein Bax into an anti-apoptotic protein. Mechanistically, we show that phosphorylation (i) enables Bax binding to pro-apoptotic BH3 proteins in solution, and (ii) prevents Bax inserting into mitochondria...
July 9, 2018: EMBO Reports
Sven Truckenbrodt, Manuel Maidorn, Dagmar Crzan, Hanna Wildhagen, Selda Kabatas, Silvio O Rizzoli
Expansion microscopy is a recently introduced imaging technique that achieves super-resolution through physically expanding the specimen by ~4×, after embedding into a swellable gel. The resolution attained is, correspondingly, approximately fourfold better than the diffraction limit, or ~70 nm. This is a major improvement over conventional microscopy, but still lags behind modern STED or STORM setups, whose resolution can reach 20-30 nm. We addressed this issue here by introducing an improved gel recipe that enables an expansion factor of ~10× in each dimension, which corresponds to an expansion of the sample volume by more than 1,000-fold...
July 9, 2018: EMBO Reports
Chiara Zurzolo
No abstract text is available yet for this article.
July 2, 2018: EMBO Reports
Christophe Olivier Schneble, Bernice Simone Elger, David Shaw
No abstract text is available yet for this article.
July 2, 2018: EMBO Reports
Ulrich Blache, Queralt Vallmajo-Martin, Edward R Horton, Julien Guerrero, Valentin Djonov, Arnaud Scherberich, Janine T Erler, Ivan Martin, Jess G Snedeker, Vincent Milleret, Martin Ehrbar
The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as factors controlling their fate, is poorly understood. Here, we study MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system in vitro We show that MSCs together with endothelial cells form micro-capillary networks specifically in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from engineered capillaries shows a prominent switch in extracellular matrix (ECM) production...
July 2, 2018: EMBO Reports
Guangzhe Ge, Ding Peng, Ziying Xu, Bao Guan, Zijuan Xin, Qun He, Yuanyuan Zhou, Xuesong Li, Liqun Zhou, Weimin Ci
Loss of 5-hydroxymethylcytosine (5hmC) occurs frequently in a wide variety of tumours, including clear-cell renal cell carcinoma (ccRCC). It remains unknown, however, whether the restoration of 5hmC patterns in tumours could have therapeutic efficacy. Here, we used sodium L-ascorbate (vitamin C, AsANa) and the oxidation-resistant form L-ascorbic acid 2-phosphate sesquimagnesium (APM) for the restoration of 5hmC patterns in ccRCC cells. At physiological concentrations, both show anti-tumour efficacy during long-term treatment in vitro and in vivo Strikingly, global 5hmC patterns in ccRCC cells after treatment resemble those of normal kidney tissue, which is observed also in treated xenograft tumours, and in primary cells from a ccRCC patient...
June 28, 2018: EMBO Reports
Deena M Leslie Pedrioli, Mario Leutert, Vera Bilan, Kathrin Nowak, Kapila Gunasekera, Elena Ferrari, Ralph Imhof, Lars Malmström, Michael O Hottiger
Despite recent mass spectrometry (MS)-based breakthroughs, comprehensive ADP-ribose (ADPr)-acceptor amino acid identification and ADPr-site localization remain challenging. Here, we report the establishment of an unbiased, multistep ADP-ribosylome data analysis workflow that led to the identification of tyrosine as a novel ARTD1/PARP1-dependent in vivo ADPr-acceptor amino acid. MS analyses of in vitro ADP-ribosylated proteins confirmed tyrosine as an ADPr-acceptor amino acid in RPS3A (Y155) and HPF1 (Y238) and demonstrated that trans -modification of RPS3A is dependent on HPF1...
June 28, 2018: EMBO Reports
Brooke Morriswood, Oliver Hoeller
No abstract text is available yet for this article.
June 27, 2018: EMBO Reports
Noa Roitenberg, Michal Bejerano-Sagie, Hana Boocholez, Lorna Moll, Filipa Carvalhal Marques, Ludmila Golodetzki, Yuval Nevo, Tayir Elami, Ehud Cohen
Reducing insulin/IGF-1 signaling (IIS) extends lifespan, promotes protein homeostasis (proteostasis), and elevates stress resistance of worms, flies, and mammals. How these functions are orchestrated across the organism is only partially understood. Here, we report that in the nematode Caenorhabditis elegans, the IIS positively regulates the expression of caveolin-1 ( cav-1 ), a gene which is primarily expressed in neurons of the adult worm and underlies the formation of caveolae, a subtype of lipid microdomains that serve as platforms for signaling complexes...
June 26, 2018: EMBO Reports
Wen-Hsin Hsu, Won-Jing Wang, Wan-Yi Lin, Yu-Min Huang, Chien-Chen Lai, Jung-Chi Liao, Hong-Chen Chen
Bipolar spindle assembly is necessary to ensure the proper progression of cell division. Loss of spindle pole integrity leads to multipolar spindles and aberrant chromosomal segregation. However, the mechanism underlying the maintenance of spindle pole integrity remains unclear. In this study, we show that the actin-binding protein adducin-1 (ADD1) is phosphorylated at S726 during mitosis. S726-phosphorylated ADD1 localizes to centrosomes, wherein it organizes into a rosette-like structure at the pericentriolar material...
June 19, 2018: EMBO Reports
Kohei Arasaki, Haruki Nagashima, Yuri Kurosawa, Hana Kimura, Naoki Nishida, Naoshi Dohmae, Akitsugu Yamamoto, Shigeru Yanagi, Yuichi Wakana, Hiroki Inoue, Mitsuo Tagaya
In fed cells, syntaxin 17 (Stx17) is associated with microtubules at the endoplasmic reticulum-mitochondria interface and promotes mitochondrial fission by determining the localization and function of the mitochondrial fission factor Drp1. Upon starvation, Stx17 dissociates from microtubules and Drp1, and binds to Atg14L, a subunit of the phosphatidylinositol 3-kinase complex, to facilitate phosphatidylinositol 3-phosphate production and thereby autophagosome formation, but the mechanism underlying this phenomenon remains unknown...
June 19, 2018: EMBO Reports
Jane Antony, Elisa Zanini, Zoe Kelly, Tuan Zea Tan, Evdoxia Karali, Mohammad Alomary, Youngrock Jung, Katherine Nixon, Paula Cunnea, Christina Fotopoulou, Andrew Paterson, Sushmita Roy-Nawathe, Gordon B Mills, Ruby Yun-Ju Huang, Jean Paul Thiery, Hani Gabra, Chiara Recchi
In ovarian cancer, the prometastatic RTK AXL promotes motility, invasion and poor prognosis. Here, we show that reduced survival caused by AXL overexpression can be mitigated by the expression of the GPI-anchored tumour suppressor OPCML Further, we demonstrate that AXL directly interacts with OPCML, preferentially so when AXL is activated by its ligand Gas6. As a consequence, AXL accumulates in cholesterol-rich lipid domains, where OPCML resides. Here, phospho-AXL is brought in proximity to the lipid domain-restricted phosphatase PTPRG, which de-phosphorylates the RTK/ligand complex...
June 15, 2018: EMBO Reports
Najla El Fissi, Manuel Rojo, Aїcha Aouane, Esra Karatas, Gabriela Poliacikova, Claudine David, Julien Royet, Thomas Rival
Charcot-Marie-Tooth disease type 2A (CMT2A) is caused by dominant alleles of the mitochondrial pro-fusion factor Mitofusin 2 (MFN2). To address the consequences of these mutations on mitofusin activity and neuronal function, we generate Drosophila models expressing in neurons the two most frequent substitutions (R94Q and R364W, the latter never studied before) and two others localizing to similar domains (T105M and L76P). All alleles trigger locomotor deficits associated with mitochondrial depletion at neuromuscular junctions, decreased oxidative metabolism and increased mtDNA mutations, but they differently alter mitochondrial morphology and organization...
June 13, 2018: EMBO Reports
Elena Marcassa, Andreas Kallinos, Jane Jardine, Emma V Rusilowicz-Jones, Aitor Martinez, Sandra Kuehl, Markus Islinger, Michael J Clague, Sylvie Urbé
USP30 is an integral protein of the outer mitochondrial membrane that counteracts PINK1 and Parkin-dependent mitophagy following acute mitochondrial depolarisation. Here, we use two distinct mitophagy reporter systems to reveal tonic suppression by USP30, of a PINK1-dependent component of basal mitophagy in cells lacking detectable Parkin. We propose that USP30 acts upstream of PINK1 through modulation of PINK1-substrate availability and thereby determines the potential for mitophagy initiation. We further show that a fraction of endogenous USP30 is independently targeted to peroxisomes where it regulates basal pexophagy in a PINK1- and Parkin-independent manner...
June 12, 2018: EMBO Reports
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