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https://www.readbyqxmd.com/read/28092672/bpgap1-spatially-integrates-jnk-erk-signaling-crosstalk-in-oncogenesis
#1
T Jiang, C Q Pan, B C Low
Simultaneous hyperactivation of stress-activated protein kinase/c-Jun N-terminal protein kinase (SAPK/JNK) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascades has been reported in carcinogenesis. However, how they are integrated to promote oncogenesis remains unknown. By analyzing breast invasive carcinoma database (The Cancer Genome Altas), we found that the mRNA expression levels of both JNK1 and ERK2 are positively correlated with the mRNA level of EEA1, an endosome associated protein, indicating the potential JNK/ERK crosstalk at endosome...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28090783/probing-the-druggability-of-membrane-bound-rab5-by-molecular-dynamics-simulations
#2
Eileen Edler, Matthias Stein
Rab5 is a small GTPase and a key regulator in early endosomal trafficking. Rab5 and its effectors are involved in a large number of infectious diseases and certain types of cancer. We performed µs atomistic molecular dynamics simulations of inactive and active full-length Rab5 anchored to a complex model bilayer with composition of the early endosome membrane. Direct interactions between the Rab5 G domain and the bilayer were observed. We found two dominant nucleotide-dependent orientations characterised by a different accessibility of the switch regions...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28089992/ankrd50-is-required-for-endosomal-recycling
#3
(no author information available yet)
No abstract text is available yet for this article.
January 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28088841/intracellular-fate-of-ureaplasma-parvum-entrapped-by-host-cellular-autophagy
#4
Fumiko Nishiumi, Michinaga Ogawa, Yukiko Nakura, Yusuke Hamada, Masahiro Nakayama, Jiro Mitobe, Atsushi Hiraide, Norio Sakai, Makoto Takeuchi, Tamotsu Yoshimori, Itaru Yanagihara
Genital mycoplasmas, including Ureaplasma spp., are among the smallest human pathogenic bacteria and are associated with preterm birth. Electron microscopic observation of U. parvum showed that these prokaryotes have a regular, spherical shape with a mean diameter of 146 nm. U. parvum was internalized into HeLa cells by clathrin-mediated endocytosis and survived for at least 14 days around the perinuclear region. Intracellular U. parvum reached endosomes in HeLa cells labeled with EEA1, Rab7, and LAMP-1 within 1 to 3 hr...
January 15, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28088463/stress-induced-egf-receptor-signaling-through-stat3-and-tumor-progression-in-triple-negative-breast-cancer
#5
Nikolas Balanis, Cathleen R Carlin
Elevated STAT3 activity is a hallmark of many epithelial carcinomas particularly in breast cancers where it is known to contribute to tumor progression through a variety of context-dependent biological responses. However, its role downstream of stress-exposed EGF receptors (EGFR) that are transactivated in endosomes independent of exogenous ligand has not been studied. This review discusses how STAT3 signaling induced by therapeutic stress in EGFR-driven triple-negative breast cancers (TNBC) might override normal epithelial homeostatic mechanisms and provide a survival advantage for tumor cells before they leave the primary tumor and spread to distant sites...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28077878/pla2g16-represents-a-switch-between-entry-and-clearance-of-picornaviridae
#6
Jacqueline Staring, Eleonore von Castelmur, Vincent A Blomen, Lisa G van den Hengel, Markus Brockmann, Jim Baggen, Hendrik Jan Thibaut, Joppe Nieuwenhuis, Hans Janssen, Frank J M van Kuppeveld, Anastassis Perrakis, Jan E Carette, Thijn R Brummelkamp
Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied. Although a range of different cell-surface receptors are bound by different picornaviruses, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#7
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077642/studies-on-the-interaction-of-tumor-derived-hd5-alpha-defensins-with-adenoviruses-and-implications-for-oncolytic-adenovirus-therapy
#8
Charles Vragniau, Jens-Martin Hübner, Peter Beidler, Sucheol Gil, Kamola Saydaminova, Zhuo-Zhuang Lu, Roma Yumul, Hongjie Wang, Maximilian Richter, Pavel Sova, Charles Drescher, Pascal Fender, André Lieber
: Defensins are small anti-microbial peptides capable of neutralizing human adenovirus (HAdV) in vitro by binding capsid proteins and blocking endosomal escape of virus. In humans, the alpha defensin HD5 is produced by specialized epithelial cells of the gastro-intestinal and genito-urinary tracts. Here we demonstrate that HD5 is also expressed as an active, secreted peptide by epithelial ovarian and lung cancer cells in situ, in patient biopsies. This finding triggered us to study the role of HD5 in infection and spread of replication-competent, oncolytic HAdV type 3 virus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077293/autophagosome-maturation-and-fusion
#9
REVIEW
Fulvio Reggiori, Christian Ungermann
Macroautophagy or simply autophagy, is a degradative pathway that delivers cytoplasmic components, including cytosol and organelles, to the lysosome in double-membrane vesicles called autophagosomes. This process is initiated at the pre-autophagosomal structure or phagophore assembly site (PAS), and involves a number of highly conserved autophagy-related (Atg) proteins. Those support the generation and conversion of an open membranous cistern known as the phagophore or isolation membrane, into a closed autophagosome...
January 8, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28076778/axl-mediates-zika-virus-entry-in-human-glial-cells-and-modulates-innate-immune-responses
#10
Laurent Meertens, Athena Labeau, Ophelie Dejarnac, Sara Cipriani, Laura Sinigaglia, Lucie Bonnet-Madin, Tifenn Le Charpentier, Mohamed Lamine Hafirassou, Alessia Zamborlini, Van-Mai Cao-Lormeau, Muriel Coulpier, Dorothée Missé, Nolwenn Jouvenet, Ray Tabibiazar, Pierre Gressens, Olivier Schwartz, Ali Amara
ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIKV entry requires the Axl ligand Gas6, which bridges ZIKV particles to glial cells. Following binding, ZIKV is internalized through clathrin-mediated endocytosis and traffics to Rab5+ endosomes to establish productive infection...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28071667/photogate-microscopy-to-track-single-molecules-in-crowded-environments
#11
Vladislav Belyy, Sheng-Min Shih, Jigar Bandaria, Yongjian Huang, Rosalie E Lawrence, Roberto Zoncu, Ahmet Yildiz
Tracking single molecules inside cells reveals the dynamics of biological processes, including receptor trafficking, signalling and cargo transport. However, individual molecules often cannot be resolved inside cells due to their high density. Here we develop the PhotoGate technique that controls the number of fluorescent particles in a region of interest by repeatedly photobleaching its boundary. PhotoGate bypasses the requirement of photoactivation to track single particles at surface densities two orders of magnitude greater than the single-molecule detection limit...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28069747/a-targeted-rnai-screen-identifies-factors-affecting-diverse-stages-of-receptor-mediated-transcytosis
#12
Bradlee Nelms, Natasha Furtado Dalomba, Wayne Lencer
Endosome transport by transcytosis is the primary mechanism by which proteins and other large cargo traverse epithelial barriers in normal tissue. Transcytosis is also essential for establishing and maintaining membrane polarity in epithelia and other polarized cells. To identify novel components of this pathway, we conducted a high-throughput RNA interference screen for factors necessary for the bidirectional transcytosis of IgG by the Fcγ receptor FcRn. This screen identified 23 genes whose suppression resulted in a reproducible decrease in FcRn-mediated transcytosis...
January 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28069241/intracellular-triggered-release-of-dna-quaternary-ammonium-polyplex-by-ultrasound
#13
Wei-Hao Liao, Ming-Yen Hsiao, Chia-Wen Lo, Hui-Shan Yang, Ming-Kuan Sun, Feng-Huei Lin, Yung Chang, Wen-Shiang Chen
2-Methacryloyloxy ethyl trimethyl ammonium chloride (TMA) is a potent polymeric plasma DNA (pDNA) carrier. The present study shows that TMA/pDNA polyplexes could be internalized into cells efficiently, but could not mediate gene transfection on its own. The transfection process of TMA/pDNA polyplexes is turned on only when ultrasound (US) was applied 4-8h after incubating TMA/pDNA polyplexes with target cells (with a gene expression 1000 times that of the immediate US group). US is a widely used physical method for gene delivery; its transfection efficiency can be significantly enhanced when combined with cationic polymer vectors...
May 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28067668/adaptor-proteins-numb-and-numbl-promote-cell-cycle-withdrawal-by-targeting-erbb2-for-degradation
#14
Maretoshi Hirai, Yoh Arita, C Jane McGlade, Kuo-Fen Lee, Ju Chen, Sylvia M Evans
Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28067008/histidine-rich-designer-peptides-of-the-lah4-family-promote-cell-delivery-of-a-multitude-of-cargo
#15
Gilles Moulay, Christian Leborgne, A James Mason, Christopher Aisenbrey, Antoine Kichler, Burkhard Bechinger
The histidine-rich designer peptides of the LAH4 family exhibit potent antimicrobial, transfection, transduction and cell-penetrating properties. They form non-covalent complexes with their cargo, which often carry a negative overall charge at pH 7.4 and include a large range of molecules and structures such as oligonucleotides, including siRNA and DNA, peptides, proteins, nanodots and adeno-associated viruses. These complexes are thought to enter the cells through an endosomal pathway where the acidification of the organelle is essential for efficient endosomal escape...
January 9, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28066811/ph-dependent-cellular-internalization-of-paramagnetic-nanoparticle
#16
Branislava Janic, Mohammed Pi Bhuiyan, James R Ewing, Meser M Ali
A hallmark of the tumor microenvironment in malignant tumor is extracellular acidosis, which can be exploited for targeted delivery of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle (NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent and pHLIP (pH Low Insertion Peptide) into the surface of a G5-PAMAM dendrimer. pHLIP showed pH-selective insertion and folding into cell membranes, but only in acidic conditions. We demonstrated that pHLIP-conjugated Gd44-G5 paramagnetic nanoparticle binds and fuses with cellular membrane at low pH, but not at normal physiological pH, and that it promotes cellular uptake...
August 26, 2016: ACS Sensors
https://www.readbyqxmd.com/read/28065471/mutations-in-atp6v1e1-or-atp6v1a-cause-autosomal-recessive-cutis-laxa
#17
Tim Van Damme, Thatjana Gardeitchik, Miski Mohamed, Sergio Guerrero-Castillo, Peter Freisinger, Brecht Guillemyn, Ariana Kariminejad, Daisy Dalloyaux, Sanne van Kraaij, Dirk J Lefeber, Delfien Syx, Wouter Steyaert, Riet De Rycke, Alexander Hoischen, Erik-Jan Kamsteeg, Sunnie Y Wong, Monique van Scherpenzeel, Payman Jamali, Ulrich Brandt, Leo Nijtmans, G Christoph Korenke, Brian H Y Chung, Christopher C Y Mak, Ingrid Hausser, Uwe Kornak, Björn Fischer-Zirnsak, Tim M Strom, Thomas Meitinger, Yasemin Alanay, Gulen E Utine, Peter K C Leung, Siavash Ghaderi-Sohi, Paul Coucke, Sofie Symoens, Anne De Paepe, Christian Thiel, Tobias B Haack, Fransiska Malfait, Eva Morava, Bert Callewaert, Ron A Wevers
Defects of the V-type proton (H(+)) ATPase (V-ATPase) impair acidification and intracellular trafficking of membrane-enclosed compartments, including secretory granules, endosomes, and lysosomes. Whole-exome sequencing in five families affected by mild to severe cutis laxa, dysmorphic facial features, and cardiopulmonary involvement identified biallelic missense mutations in ATP6V1E1 and ATP6V1A, which encode the E1 and A subunits, respectively, of the V1 domain of the heteromultimeric V-ATPase complex. Structural modeling indicated that all substitutions affect critical residues and inter- or intrasubunit interactions...
December 29, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28065306/measuring-abscission-spatiotemporal-dynamics-using-quantitative-high-resolution-microscopy
#18
O Gershony, S Sherman, S Adar, I Segal, D Nachmias, I Goliand, N Elia
The spatiotemporal characteristics of ESCRT (Endosomal Sorting Complex Required for Transport)-mediated mammalian cytokinetic abscission have been studied in recent years using quantitative high-resolution light microscopy techniques. Here we describe how to apply spinning disk live cell imaging and structured illumination microscopy (SIM) to define the dynamics and structural organization of abscission and of proteins involved in abscission in a quantitative manner. We further provide a protocol to correlate the structural data, obtained by SIM, to the dynamic information obtained by live cell recordings...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28063015/innate-immunity-against-legionella-pneumophila-during-pulmonary-infections-in-mice
#19
REVIEW
Bonggoo Park, Gayoung Park, Jiyoung Kim, Seon Ah Lim, Kyung-Mi Lee
Legionella pneumophila is an etiological agent of the severe pneumonia known as Legionnaires' disease (LD). This gram-negative bacterium is thought to replicate naturally in various freshwater amoebae, but also replicates in human alveolar macrophages. Inside host cells, legionella induce the production of non-endosomal replicative phagosomes by injecting effector proteins into the cytosol. Innate immune responses are first line defenses against legionella during early phases of infection, and distinguish between legionella and host cells using germline-encoded pattern recognition receptors such as Toll-like receptors , NOD-like receptors, and RIG-I-like receptors, which sense pathogen-associated molecular patterns that are absent in host cells...
January 6, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28062852/a-proteomic-approach-to-identify-endosomal-cargoes-controlling-cancer-invasiveness
#20
Jesica Diaz-Vera, Sarah Palmer, Juan Ramon Hernandez-Fernaud, Emmanuel Dornier, Louise E Mitchell, Iain Macpherson, Joanne Edwards, Sara Zanivan, Jim C Norman
We have previously shown that Rab17 - a small GTPase associated with epithelial polarity - is specifically suppressed by ERK2 signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this are not known. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp-8 is associated with Rab17 at late endosomes...
January 6, 2017: Journal of Cell Science
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