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https://www.readbyqxmd.com/read/27923836/the-swi-snf-complex-protein-snr1-is-a-tumor-suppressor-in-drosophila-imaginal-tissues
#1
Gengqiang Xie, Hanqing Chen, Dongyu Jia, Zhiqiang Shu, William Hunt Palmer, Yi-Chun Huang, Xiankun Zeng, Steven X Hou, Renjie Jiao, Wu-Min Deng
Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27922607/endocytosis-following-dopamine-d2-receptor-activation-is-critical-for-neuronal-activity-and-dendritic-spine-formation-via-rabex-5-pdgfr%C3%AE-signaling-in-striatopallidal-medium-spiny-neurons
#2
N Shioda, Y Yabuki, Y Wang, M Uchigashima, T Hikida, T Sasaoka, H Mori, M Watanabe, M Sasahara, K Fukunaga
Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. Here, we report that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-regulated kinase (ERK) activation and dendritic spine formation through Rabex-5/platelet-derived growth factor receptor-β (PDGFRβ)-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early-endosome formation...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27917878/spatiotemporal-control-of-interferon-induced-jak-stat-signalling-and-gene-transcription-by-the-retromer-complex
#3
Daniela Chmiest, Nanaocha Sharma, Natacha Zanin, Christine Viaris de Lesegno, Massiullah Shafaq-Zadah, Vonick Sibut, Florent Dingli, Philippe Hupé, Stephan Wilmes, Jacob Piehler, Damarys Loew, Ludger Johannes, Gideon Schreiber, Christophe Lamaze
Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of the IFNAR complex are differentially sorted by the retromer at the early endosome. Binding of the retromer VPS35 subunit to IFNAR2 results in IFNAR2 recycling to the plasma membrane, whereas IFNAR1 is sorted to the lysosome for degradation...
December 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27916608/functional-properties-of-hepatocytes-in-vitro-are-correlated-with-cell-polarity-maintenance
#4
Anja Zeigerer, Anne Wuttke, Giovanni Marsico, Sarah Seifert, Yannis Kalaidzidis, Marino Zerial
Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect the molecular mechanisms underlying the structure and function of the liver in vivo. However, this approach relies on appropriate in vitro cell culture systems that can recapitulate the cell biological and metabolic features of the hepatocytes in the liver whilst being accessible to experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy and quantitative image analysis to compare two primary hepatocyte culture systems, monolayer and collagen sandwich, with respect to the distribution of two distinct populations of early endosomes (APPL1 and EEA1-positive), endocytic capacity, metabolic and signaling activities...
December 1, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#5
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27909244/cd4-down-regulation-by-hiv-1-nef-reveals-distinct-roles-for-%C3%AE-1-and-%C3%AE-2-subunits-of-ap-1-complex-in-protein-trafficking
#6
Lucas A Tavares, Eulália M L da Silva, Mara E da Silva-Januário, Yunan C Januário, Julianne V de Cavalho, Érika S Czernisz, Gonzalo A Mardones, Luis L P daSilva
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and subsequent target to lysosomes. Herein, we report that this lysosomal targeting requires a variant of the AP-1 comprising the isoform 2 of γ-adaptin...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27899655/visualization-of-self-delivering-hydrophobically-modified-sirna-cellular-internalization
#7
Socheata Ly, Deanna M Navaroli, Marie-Cécile Didiot, James Cardia, Lakshmipathi Pandarinathan, Julia F Alterman, Kevin Fogarty, Clive Standley, Lawrence M Lifshitz, Karl D Bellve, Matthieu Prot, Dimas Echeverria, Silvia Corvera, Anastasia Khvorova
siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of asymmetric, chemically stabilized, cholesterol-modified siRNAs (sd-rxRNAs(®)) that efficiently enter cells and tissues without the need for formulation. We demonstrate that uptake is rapid with significant membrane association within minutes of exposure followed by the formation of vesicular structures and internalization...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899503/postreplication-roles-of-the-brucella-virb-type-iv-secretion-system-uncovered-via-conditional-expression-of-the-virb11-atpase
#8
Erin P Smith, Cheryl N Miller, Robert Child, Jennifer A Cundiff, Jean Celli
: Brucella abortus, the bacterial agent of the worldwide zoonosis brucellosis, primarily infects host phagocytes, where it undergoes an intracellular cycle within a dedicated membrane-bound vacuole, the Brucella-containing vacuole (BCV). Initially of endosomal origin (eBCV), BCVs are remodeled into replication-permissive organelles (rBCV) derived from the host endoplasmic reticulum, a process that requires modulation of host secretory functions via delivery of effector proteins by the Brucella VirB type IV secretion system (T4SS)...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27899210/comparative-analysis-of-the-internalization-of-the-macrophage-receptor-sialoadhesin-in-human-and-mouse-primary-macrophages-and-cell-lines
#9
Marjorie De Schryver, Annelies Leemans, Isabel Pintelon, Davie Cappoen, Louis Maes, Guy Caljon, Paul Cos, Peter L Delputte
Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs...
November 21, 2016: Immunobiology
https://www.readbyqxmd.com/read/27899122/endocytosed-nanoparticles-hold-endosomes-and-stimulate-binucleated-cells-formation
#10
Lin Xia, Weihong Gu, Mingyi Zhang, Ya-Nan Chang, Kui Chen, Xue Bai, Lai Yu, Juan Li, Shan Li, Gengmei Xing
BACKGROUND: Nanotechnology developed rapidly in cellular diagnosis and treatment, the endocytic system was an important pathway for targeting cell. In the research of developing macrophages as drug carriers or important therapeutic targets, an interesting phenomenon, internalized nanoparticles induced to form binucleated macrophages, was found although the particles dose did not cause obvious cytotoxicity. RESULTS: Under 25 μg/ml, internalized 30 nm polystyrene beads(30 nm Ps nanoparticles) induced the formation of binucleated macrophages when they entered into endosomes via the endocytic pathway...
November 29, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27895154/kidney-tubular-ablation-of-ocrl-inpp5b-phenocopies-lowe-syndrome-tubulopathy
#11
Kazunori Inoue, Daniel M Balkin, Lijuan Liu, Ramiro Nandez, Yumei Wu, Xuefei Tian, Tong Wang, Robert Nussbaum, Pietro De Camilli, Shuta Ishibe
Lowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of Ocrl in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule-specific inactivation of Inpp5b on a global Ocrl-knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27895104/bin1-and-cd2ap-polarise-the-endocytic-generation-of-beta-amyloid
#12
Florent Ubelmann, Tatiana Burrinha, Laura Salavessa, Ricardo Gomes, Cláudio Ferreira, Nuno Moreno, Cláudia Guimas Almeida
The mechanisms driving pathological beta-amyloid (Aβ) generation in late-onset Alzheimer's disease (AD) are unclear. Two late-onset AD risk factors, Bin1 and CD2AP, are regulators of endocytic trafficking, but it is unclear how their endocytic function regulates Aβ generation in neurons. We identify a novel neuron-specific polarisation of Aβ generation controlled by Bin1 and CD2AP We discover that Bin1 and CD2AP control Aβ generation in axonal and dendritic early endosomes, respectively. Both Bin1 loss of function and CD2AP loss of function raise Aβ generation by increasing APP and BACE1 convergence in early endosomes, however via distinct sorting events...
November 28, 2016: EMBO Reports
https://www.readbyqxmd.com/read/27882950/neutralization-mechanism-of-a-highly-potent-antibody-against-zika-virus
#13
Shuijun Zhang, Victor A Kostyuchenko, Thiam-Seng Ng, Xin-Ni Lim, Justin S G Ooi, Sebastian Lambert, Ter Yong Tan, Douglas G Widman, Jian Shi, Ralph S Baric, Shee-Mei Lok
The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27879337/interactions-between-melanin-enzymes-and-their-atypical-recruitment-to-the-secretory-pathway-by-palmitoylation
#14
Srijana Upadhyay, Xinping Xu, Xiaorong Lin
: Melanins are biopolymers that confer coloration and protection to the host organism against biotic or abiotic insults. The level of protection offered by melanin depends on its biosynthesis and its subcellular localization. Previously, we discovered that Aspergillus fumigatus compartmentalizes melanization in endosomes by recruiting all melanin enzymes to the secretory pathway. Surprisingly, although two laccases involved in the late steps of melanization are conventional secretory proteins, the four enzymes involved in the early steps of melanization lack a signal peptide or a transmembrane domain and are thus considered "atypical" secretory proteins...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27875556/mxa-is-a-novel-regulator-of-endosome-associated-transcriptional-signaling-by-bone-morphogenetic-proteins-4-and-9-bmp4-and-bmp9
#15
Huijuan Yuan, Pravin B Sehgal
There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2...
2016: PloS One
https://www.readbyqxmd.com/read/27875067/transiently-expressed-atg16l1-inhibits-autophagosome-biogenesis-and-aberrantly-targets-rab11-positive-recycling-endosomes
#16
Jiehua Li, Zhixia Chen, Michael T Stang, Wentao Gao
The membrane source for autophagosome biogenesis is an unsolved mystery in the study of autophagy. ATG16L1 forms a complex with ATG12-ATG5 (the ATG16L1 complex). The ATG16L1 complex is recruited to autophagic membranes to convert MAP1LC3B-I to MAP1LC3B-II. The ATG16L1 complex dissociates from the phagophore before autophagosome membrane closure. Thus, ATG16L1 can be used as an early event marker for the study of autophagosome biogenesis. We found that among 3 proteins in the ATG16L1 complex, only ATG16L1 formed puncta-like structures when transiently overexpressed...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27872256/the-endosomal-transcriptional-regulator-rnf11-integrates-degradation-and-transport-of-egfr
#17
Sandra Scharaw, Murat Iskar, Alessandro Ori, Gaelle Boncompain, Vibor Laketa, Ina Poser, Emma Lundberg, Franck Perez, Martin Beck, Peer Bork, Rainer Pepperkok
Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane...
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27867015/cmtm3-decreases-egfr-expression-and-egf-mediated-tumorigenicity-by-promoting-rab5-activity-in-gastric-cancer
#18
Wanqiong Yuan, Baocai Liu, Xiaolin Wang, Ting Li, Hui Xue, Xiaoning Mo, Shuli Yang, Shigang Ding, Wenling Han
CMTM3 (CKLF-like MARVEL transmembrane domain containing 3), a tumor suppressor gene, is involved in multiple types of malignancies. CMTM3 knockdown promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway. Strong epidermal growth factor receptor1 (EGFR) expression is significantly associated with tumor metastasis and poor outcomes of gastric cancer patients. In this paper, we show that CMTM3 suppresses epidermal growth factor (EGF)-mediated migration and STAT3 signaling, downregulates EGFR expression via accelerating EGFR degradation in gastric cancer cells...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27864431/apol1-mediated-cell-injury-involves-disruption-of-conserved-trafficking-processes
#19
Etty Kruzel-Davila, Revital Shemer, Ayala Ofir, Ira Bavli-Kertselli, Ilona Darlyuk-Saadon, Pazit Oren-Giladi, Walter G Wasser, Daniella Magen, Eid Zaknoun, Maya Schuldiner, Adi Salzberg, Daniel Kornitzer, Zvonimir Marelja, Matias Simons, Karl Skorecki
APOL1 harbors C-terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub-Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D...
November 18, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27863541/cellular-endocytic-compartment-localization-of-expressed-canine-cd1-molecules
#20
Mette Schjaerff, Stefan M Keller, Verena K Affolter, Annemarie T Kristensen, Peter F Moore
CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which recognize and present a variety of foreign- and self-lipid antigens to T-cells. Humans have five different CD1 isoforms that survey distinct cellular compartments allowing for recognition of a large repertoire of lipids. The canine CD1 family consists of seven functional CD1 molecules (canine CD1a2, CD1a6, CD1a8, CD1a9, CD1b, CD1c and CD1e) and one presumed non-functional isoform (canine CD1d) due to a disrupted gene structure...
December 2016: Veterinary Immunology and Immunopathology
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