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https://www.readbyqxmd.com/read/27899443/rab43-facilitates-cross-presentation-of-cell-associated-antigens-by-cd8%C3%AE-dendritic-cells
#1
Nicole M Kretzer, Derek J Theisen, Roxane Tussiwand, Carlos G Briseño, Gary E Grajales-Reyes, Xiaodi Wu, Vivek Durai, Jörn Albring, Prachi Bagadia, Theresa L Murphy, Kenneth M Murphy
In this study, to examine cross-presentation by classical dendritic cells (DCs; cDCs), we evaluated the role of RAB43, a protein found to be selectively expressed by Batf3-dependent CD8α(+) and CD103(+) compared with other DC subsets and immune lineages. Using a specific monoclonal antibody, we localized RAB43 expression to the Golgi apparatus and LAMP1(-) cytoplasmic vesicles. Mice with germline or conditional deletion of Rab43 are viable and fertile and have normal development of cDCs but show a defect for in vivo and in vitro cross-presentation of cell-associated antigen...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27875583/k63-linked-ubiquitination-targets-toxoplasma-gondii-for-endo-lysosomal-destruction-in-ifn%C3%AE-stimulated-human-cells
#2
Barbara Clough, Joseph D Wright, Pedro M Pereira, Elizabeth M Hirst, Ashleigh C Johnston, Ricardo Henriques, Eva-Maria Frickel
Toxoplasma gondii is the most common protozoan parasitic infection in man. Gamma interferon (IFNγ) activates haematopoietic and non-haematopoietic cells to kill the parasite and mediate host resistance. IFNγ-driven host resistance pathways and parasitic virulence factors are well described in mice, but a detailed understanding of pathways that kill Toxoplasma in human cells is lacking. Here we show, that contrary to the widely held belief that the Toxoplasma vacuole is non-fusogenic, in an immune-stimulated environment, the vacuole of type II Toxoplasma in human cells is able to fuse with the host endo-lysosomal machinery leading to parasite death by acidification...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27832934/abcb1-2677-g-t-a-variant-enhances-chemosensitivity-to-anti-cancer-agents-acting-on-microtubule-dynamics-through-lamp1-inhibition
#3
Woo Sun Kwon, Sun Young Rha, Hei-Cheul Jeung, Joong Bae Ahn, Jae -Joon Jung, Dong Hyuk Ki, Tae Soo Kim, Hyun Cheol Chung
Overexpression of ABCB1 associated with single nucleotide variants in cancers was reported to encode a protein responsible for drug resistance. We studied chemosensitivity-related genes associated with ABCB1 2677G>T/A variant. The associated genes were identified based on the results of the significance analysis of microarray, and then prediction accuracy was evaluated using the prediction analysis of microarray. Functional assay of the selected gene was performed by using siRNA and drug accumulation study...
November 7, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27788920/lamp1-expression-is-associated-with-malignant-behaviours-and-predicts-unfavourable-prognosis-in-laryngeal-squamous-cell-carcinoma-lscc
#4
Meiping Lu, Huijun Zhu, Xudong Wang, Dawei Zhang, Lin Xiong, Jin Zhu, Yuan Mao, Jianfeng Qiang
Lysosome-associated membrane protein-1 (LAMP1) has been suggested to play complicated roles in cancer development and metastasis. The aim of this study was to explore the expression of LAMP1 in laryngeal squamous cell carcinoma (LSCC) and investigate the relationship between LAMP1 expression and clinicopathological characteristics in LSCC patients. One-step quantitative reverse transcription PCR (qPCR) tests (20 fresh LSCC and non-cancerous tissue samples) and immunohistochemistry (IHC) analyses (137 paraffin-embedded LSCC and non-cancerous tissue samples) were performed to evaluate the LAMP1 expression in both mRNA and protein levels...
October 24, 2016: Pathology
https://www.readbyqxmd.com/read/27780934/patient-fibroblasts-derived-induced-neurons-demonstrate-autonomous-neuronal-defects-in-adult-onset-krabbe-disease
#5
Su Min Lim, Byung-Ok Choi, Seong-Il Oh, Won Jun Choi, Ki-Wook Oh, Minyeop Nahm, Yuanchao Xue, Jae Hyeok Choi, Ji Young Choi, Young-Eun Kim, Ki Wha Chung, Xiang-Dong Fu, Chang-Seok Ki, Seung Hyun Kim
Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by defective β-galactosylceramidase (GALC), a lysosomal enzyme responsible for cleavage of several key substrates including psychosine. Accumulation of psychosine to the cytotoxic levels in KD patients is thought to cause dysfunctions in myelinating glial cells based on a comprehensive study of demyelination in KD. However, recent evidence suggests myelin-independent neuronal death in the murine model of KD, thus indicating defective GALC in neurons as an autonomous mechanism for neuronal cell death in KD...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27773683/autophagy-lysosome-dysfunction-is-involved-in-a%C3%AE-deposition-in-stz-induced-diabetic-rats
#6
Lou-Yan Ma, Ya-Li Lv, Kang Huo, Jie Liu, Su-Hang Shang, Yu-Lang Fei, Yan-Bo Li, Bei-Yu Zhao, Meng Wei, Yong-Ning Deng, Qiu-Min Qu
β-Amyloid (Aβ) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce Aβ deposition in the brain, but the mechanism is not fully elucidated. Autophagy-lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether autophagy-lysosome is related to Aβ1-42 clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p<0...
October 20, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27771328/holocrine-secretion-of-sebum-is-a-unique-dnase2-dependent-mode-of-programmed-cell-death
#7
Heinz Fischer, Judith Fumicz, Heidemarie Rossiter, Markus Napirei, Maria Buchberger, Erwin Tschachler, Leopold Eckhart
Sebaceous glands produce sebum via holocrine secretion, a largely uncharacterized mode of programmed cell death that contributes to the homeostasis and barrier function of the skin. To determine the mechanism of DNA degradation during sebocyte cell death, we have inactivated candidate DNA-degrading enzymes by targeted gene deletions in mice. DNase1 and DNase1L2 were dispensable for nuclear DNA degradation in sebocytes. By contrast, epithelial cell-specific deletion of lysosomal DNase2 blocked DNA degradation in these cells...
October 19, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27742708/a-new-molecular-link-between-defective-autophagy-and-erythroid-abnormalities-in-chorea-acanthocytosis
#8
Francesca Lupo, Elena Tibaldi, Alessandro Matte, Alok K Sharma, Anna Maria Brunati, Seth L Alper, Carlo Zancanaro, Donatella Benati, Angela Siciliano, Mariarita Bertoldi, Francesca Zonti, Alexander Storch, Ruth H Walker, Adrian Danek, Benedikt Bader, Andreas Hermann, Lucia De Franceschi
Chorea-acanthocytosis is one of the hereditary neurodegenerative disorders known as the neuroacanthocytoses. Chorea-acanthocytosis is characterized by circulating acanthocytes deficient in chorein, a protein of unknown function. We report here for the first time that chorea-acanthocytosis red-cells are characterized by impaired autophagy, with cytoplasmic accumulation of active Lyn and of autophagy-related proteins Ulk1, Atg7. In chorea-acanthocytosis erythrocytes, active Lyn is sequestered by HSP90-70 to form high-molecular-weight complexes that stabilize and protect Lyn from its proteasomal degradation, contributing to toxic Lyn accumulation...
October 14, 2016: Blood
https://www.readbyqxmd.com/read/27727322/identification-of-putative-receptors-for-the-novel-adipokine-ctrp3-using-ligand-receptor-capture-technology
#9
Ying Li, Tammy Ozment, Gary L Wright, Jonathan M Peterson
METHODS: We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment with CTRP3-FLAG protein as ligand and insulin as a control ligand was performed on the H4IIE rat hepatoma cell line. RESULTS: Initial analysis demonstrated efficient coupling of TriCEPS to CTRP3. Further, flow cytometry analysis (FACS) demonstrated successful oxidation and crosslinking of CTRP3-TriCEPS and Insulin-TriCEPS complexes to cell surface glycans...
2016: PloS One
https://www.readbyqxmd.com/read/27707803/a-novel-trappc11-mutation-in-two-turkish-families-associated-with-cerebral-atrophy-global-retardation-scoliosis-achalasia-and-alacrima
#10
Katrin Koehler, Miroslav P Milev, Keshika Prematilake, Felix Reschke, Susann Kutzner, Ramona Jühlen, Dana Landgraf, Eda Utine, Filiz Hazan, Gulden Diniz, Markus Schuelke, Angela Huebner, Michael Sacher
BACKGROUND: Triple A syndrome (MIM #231550) is associated with mutations in the AAAS gene. However, about 30% of patients with triple A syndrome symptoms but an unresolved diagnosis do not harbour mutations in AAAS. OBJECTIVE: Search for novel genetic defects in families with a triple A-like phenotype in whom AAAS mutations are not detected. METHODS: Genome-wide linkage analysis, whole-exome sequencing and functional analyses were used to discover and verify a novel genetic defect in two families with achalasia, alacrima, myopathy and further symptoms...
October 5, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27697285/vitamin-d3-regulates-lamp3-expression-in-monocyte-derived-dendritic-cells
#11
L Malaguarnera, A Marsullo, K Zorena, G Musumeci, M Di Rosa
The family of lysosome-associated membrane proteins (LAMPs) encompassing LAMP1, LAMP2 and DC-LAMP (LAMP3) are the major constituents of the glycoconjugates coat present on the inside of the lysosomal membrane. LAMP3 is highly expressed only in certain cell types and during the differentiation stages. Its expression is linked the maturation of dendritic cells, inflammation, poor prognosis of certain tumors, and the locus where it is encoded was identified as a risk factor for Parkinson's disease (PD). Here, we investigated the capacity of Vitamin D3 to modulate the expression of LAMP3 during the dendritic cells differentiation and maturation...
September 28, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27687594/role-of-autophagy-and-lysosomal-drug-sequestration-in-acquired-resistance-to-doxorubicin-in-mcf-7-cells
#12
Baoqing Guo, Adam Tam, Stacey A Santi, Amadeo M Parissenti
BACKGROUND: The roles and mechanisms involved in starvation-induced autophagy in mammalian cells have been extensively studied. However, less is known about the potential role for autophagy as a survival pathway in acquired drug resistance in cancer cells under nutrient-rich conditions. METHODS: We selected MCF-7 breast tumor cells for survival in increasing concentrations of doxorubicin and assessed whether the acquisition of doxorubicin resistance was accompanied by changes in doxorubicin and lysosome localization and the activation of autophagy, as assessed by laser scanning confocal microscopy with or without immunohistochemical approaches...
September 29, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27667454/-zinc-dependent-metalloprotease-1-zmp1-inhibits-the-proliferation-and-phagosome-lysosome-fusion-of-mouse-macrophage-raw264-7
#13
Chencheng Fang, Jiming Zhang, Nan Lu, Peng Li, Yu Fan, Yuexi Kang, Chun Yang, Yonglin He
Objective To observe the effect of zinc-dependent metalloprotease 1 (Zmp1) of Bacillus Calmette Guerin vaccine (BCG) on the proliferation and phagosome-lysosome fusion of RAW264.7 mouse macrophage. Methods Zmp1 was expressed in E.coli BL21 (DE3) and purified by metal chelate magnetic beads. RAW264.7 cells were incubated with the purified Zmp1. Cell proliferation was detected at 0, 24, 48, 72 and 96 hours by cell counting kit-8 (CCK-8) assay and cell cycle distribution was detected by flow cytometry (FCM). The formation of phagosome was induced after RAW264...
October 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27664420/lysosomal-membrane-glycoproteins-bind-cholesterol-and-contribute-to-lysosomal-cholesterol-export
#14
Jian Li, Suzanne R Pfeffer
LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon's disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, and its expression improves tissue function in models of aging. We show here that human LAMP1 and LAMP2 bind cholesterol in a manner that buries the cholesterol 3β-hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that export cholesterol from lysosomes...
September 24, 2016: ELife
https://www.readbyqxmd.com/read/27605678/role-of-lamp1-binding-and-ph-sensing-by-the-spike-complex-of-lassa-virus
#15
Hadas Cohen-Dvashi, Hadar Israeli, Orly Shani, Aliza Katz, Ron Diskin
: To effectively infect cells, Lassa virus needs to switch in an endosomal compartment from its primary receptor, α-dystroglycan, to a protein termed LAMP1. A unique histidine triad on the surface of the receptor-binding domain from the glycoprotein spike complex of Lassa virus is important for LAMP1 binding. Here we investigate mutated spikes that have an impaired ability to interact with LAMP1 and show that although LAMP1 is important for efficient infectivity, it is not required for spike-mediated membrane fusion per se Our studies reveal important regulatory roles for histidines from the triad in sensing acidic pH and preventing premature spike triggering...
November 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27586257/heat-shock-factor-4-regulates-lens-epithelial-cell-homeostasis-by-working-with-lysosome-and-anti-apoptosis-pathways
#16
Xiukun Cui, Huiyuan Liu, Jing Li, Kangwen Guo, Wenxiu Han, Yi Dong, Simin Wan, Xuance Wang, Panpan Jia, Shulian Li, Yuanfang Ma, Jun Zhang, Hongmei Mu, Yanzhong Hu
Activation of Heat shock factor 4-mediated heat shock response is closely associated with postnatal lens development. HSF4 controls the expression of small heat shock proteins (e.g. HSP25 and CRYAB) in lens epithelial cells. However, their roles in modulating lens epithelium homeostasis remain unclear. In this paper, we find that HSF4 is developmentally expressed in mouse lens epithelium and fiber tissue. HSF4 and alpha B-crystallin can selectively protect lens epithelial cells from cisplatin and H2O2 induced apoptosis by stabilizing mitochondrial membrane potential (ΔYm) and reducing ROS production...
October 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27563301/antibody-dependent-nk-cell-activation-is-associated-with-late-kidney-allograft-dysfunction-and-the-complement-independent-alloreactive-potential-of-donor-specific-antibodies
#17
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27550070/rab24-interacts-with-the-rab7-rab-interacting-lysosomal-protein-complex-to-regulate-endosomal-degradation
#18
Celina Amaya, Rodrigo D Militello, Sebastián D Calligaris, María I Colombo
Endocytosis is a multistep process engaged in extracellular molecules internalization. Several proteins including the Rab GTPases family coordinate the endocytic pathway. The small GTPase Rab7 is present in late endosome (LE) compartments being a marker of endosome maturation. The Rab interacting lysosomal protein (RILP) is a downstream effector of Rab7 that recruits the functional dynein/dynactin motor complex to late compartments. In the present study, we have found Rab24 as a component of the endosome-lysosome degradative pathway...
August 23, 2016: Traffic
https://www.readbyqxmd.com/read/27509031/characterization-of-laminin-binding-integrin-internalization-in-prostate-cancer-cells
#19
Lipsa Das, Todd A Anderson, Jaime M C Gard, Isis C Sroka, Stephanie R Strautman, Raymond B Nagle, Colm Morrissey, Beatrice S Knudsen, Anne E Cress
Laminin binding integrins α6 (CD49f) and α3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modelling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, α6 integrin internalized with a rate constant (kactual ) of 3.25min(-1) , 3-fold faster than α3 integrin (1...
August 10, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27490928/tmem166-eva1a-interacts-with-atg16l1-and-induces-autophagosome-formation-and-cell-death
#20
Jia Hu, Ge Li, Liujing Qu, Ning Li, Wei Liu, Dan Xia, Beiqi Hongdu, Xin Lin, Chentong Xu, Yaxin Lou, Qihua He, Dalong Ma, Yingyu Chen
The formation of the autophagosome is controlled by an orderly action of ATG proteins. However, how these proteins are recruited to autophagic membranes remain poorly clarified. In this study, we have provided a line of evidence confirming that EVA1A (eva-1 homolog A)/TMEM166 (transmembrane protein 166) is associated with autophagosomal membrane development. This notion is based on dotted EVA1A structures that colocalize with ZFYVE1, ATG9, LC3B, ATG16L1, ATG5, STX17, RAB7 and LAMP1, which represent different stages of the autophagic process...
August 4, 2016: Cell Death & Disease
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