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Recycling endosomes

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https://www.readbyqxmd.com/read/28817705/cell-surface-dynamics-and-cellular-distribution-of-endogenous-fcrn
#1
Lena D'Hooghe, Andrew D Chalmers, Sam Heywood, Paul Whitley
A major role for FcRn is the salvage of pinocytosed IgG and albumin from a degradative fate in lysosomes. FcRn achieves this by binding IgG in a pH-dependent manner in acidic endosomes and recycling it to the plasma membrane to be released at neutral pH. This is important in maintaining high serum IgG and albumin levels and has the potential to be exploited to modulate the pharmacokinetics of antibody-based therapeutics. Although FcRn is responsible for the recycling of IgG, the dynamic behaviour of endogenous FcRn is not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/28815171/functional-analysis-of-na-h-exchanger-9-variants-identified-in-patients-with-autism-and-epilepsy
#2
Hari Prasad, James Osei-Owusu, Rajini Rao
Na(+)/H(+) exchanger isoform 9, NHE9, finely tunes the pH within the endosomal lumen to regulate cargo trafficking and turnover. In patients with autism, genetic approaches have revealed deletions, truncations and missense mutations in the gene encoding NHE9 (SLC9A9). To help establish causality, functional evaluation is needed to distinguish pathogenic mutations from harmless polymorphisms. Here, we evaluated three previously uncharacterized NHE9 variants, P117T, D496N, and Q609K reported in patients with autism and epilepsy...
April 2017: Matters (Zur)
https://www.readbyqxmd.com/read/28813417/cmtm6-maintains-the-expression-of-pd-l1-and-regulates-anti-tumour-immunity
#3
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid Y N Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik, Joseph A Trapani, Jonathan Cebon, Paul J Lehner, Mark A Dawson
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28808191/shunts-channels-and-lipoprotein-endosomal-traffic-a-new-model-of-cholesterol-homeostasis-in-the-hepatocyte
#4
Robert Scott Kiss, Allan Sniderman
The liver directs cholesterol metabolism in the organism. All the major fluxes of cholesterol within the body involve the liver: dietary cholesterol is directed to the liver; cholesterol from peripheral cells goes to the liver; the liver is a major site of cholesterol synthesis for the organism; cholesterol is secreted from the liver within the bile, within apoB lipoproteins and translocated to nascent HDL. The conventional model of cholesterol homeostasis posits that cholesterol from any source enters a common, rapidly exchangeable pool within the cell, which is in equilibrium with a regulatory pool...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28798148/ubiquitination-of-basal-vegfr2-regulates-signal-transduction-and-endothelial-function
#5
Gina A Smith, Gareth W Fearnley, Izma Abdul-Zani, Stephen B Wheatcroft, Darren C Tomlinson, Michael A Harrison, Sreenivasan Ponnambalam
Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulates signal transduction and angiogenesis but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated response by endothelial cells...
August 10, 2017: Biology Open
https://www.readbyqxmd.com/read/28797837/endosomal-sort-of-signaling-control-the-role-of-escrt-machinery-in-regulation-of-receptor-mediated-signaling-pathways
#6
REVIEW
Ewelina Szymanska, Noga Budick-Harmelin, Marta Miaczynska
The endosomal sorting complexes required for transport (ESCRTs) machinery consists of four protein assemblies (ESCRT-0 to -III subcomplexes) which mediate various processes of membrane remodeling in the cell. In the endocytic pathway, ESCRTs sort cargo destined for degradation into intraluminal vesicles (ILVs) of endosomes. Cargos targeted by ESCRTs include various signaling molecules, mainly internalized cell-surface receptors but also some cytosolic proteins. It is therefore expected that aberrant trafficking caused by ESCRT dysfunction affects different signaling pathways...
August 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28794269/the-fc%C3%AE%C2%B5ri-signaling-cascade-and-integrin-trafficking-converge-at-patterned-ligand-surfaces
#7
Devin L Wakefield, David Holowka, Barbara Baird
We examined the spatial targeting of early and downstream signaling mediated by the IgE receptor (FcεRI) in RBL mast cells utilizing surface-patterned 2,4 dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge-concentrated for DNP-BSA...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28791638/activation-of-endosome-associated-inert-egf-receptor-following-internalization
#8
Yi Wang, Sukhmani Billing, Zhixiang Wang
Our current understanding of endosomal signaling is incomplete given our inability to generate endosomal signals in isolation from plasma membrane signals. We present a novel method to specifically activate epidermal growth factor (EGF) receptor (EGFR) following its internalization into endosomes. This method will allow us to address questions such as whether endosomal signaling is sufficient to activate signal transduction pathways and produce biological responses. In this method, the cells are treated with EGF in the presence of AG1478, a specific EGFR tyrosine kinase inhibitor, and monensin, which blocks recycling of EGFR...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28771332/cathepsin-mediated-cleavage-of-peptides-from-peptide-amphiphiles-leads-to-enhanced-intracellular-peptide-accumulation
#9
Handan Acar, Ravand Samaeekia, Matthew R Schnorenberg, Dibyendu K Sasmal, Jun Huang, Matthew V Tirrell, James L LaBelle
Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein-protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide Amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation and PA monomers are internalized via endocytosis...
August 3, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28768685/genetic-dissection-of-early-endosomal-recycling-highlights-a-torc1-independent-role-for-rag-gtpases
#10
Chris MacDonald, Robert C Piper
Endocytosed cell surface membrane proteins rely on recycling pathways for their return to the plasma membrane. Although endosome-to-plasma membrane recycling is critical for many cellular processes, much of the required machinery is unknown. We discovered that yeast has a recycling route from endosomes to the cell surface that functions efficiently after inactivation of the sec7-1 allele of Sec7, which controls transit through the Golgi. A genetic screen based on an engineered synthetic reporter that exclusively follows this pathway revealed that recycling was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6...
August 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28757549/updated-insight-into-the-physiological-and-pathological-roles-of-the-retromer-complex
#11
REVIEW
Yakubu Saddeeq Abubakar, Wenhui Zheng, Stefan Olsson, Jie Zhou
Retromer complexes mediate protein trafficking from the endosomes to the trans-Golgi network (TGN) or through direct recycling to the plasma membrane. In yeast, they consist of a conserved trimer of the cargo selective complex (CSC), Vps26-Vps35-Vps29 and a dimer of sorting nexins (SNXs), Vps5-Vps17. In mammals, the CSC interacts with different kinds of SNX proteins in addition to the mammalian homologues of Vps5 and Vps17, which further diversifies retromer functions. The retromer complex plays important roles in many cellular processes including restriction of invading pathogens...
July 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28741645/inflammasome-and-autophagy-regulation-a-two-way-street
#12
Qian Sun, Jie Fan, Timothy R Billiar, Melanie J Scott
Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by non-infectious, endogenous agents can be detrimental, and if excessive can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a NOD-like receptor (NLR), an adaptor protein (ASC) and procaspase-1...
July 24, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28740133/spatial-cycles-mediated-by-unc119-solubilisation-maintain-src-family-kinases-plasma-membrane-localisation
#13
Antonios D Konitsiotis, Lisaweta Roßmannek, Angel Stanoev, Malte Schmick, Philippe I H Bastiaens
The peripheral membrane proto-oncogene Src family protein tyrosine kinases relay growth factor signals to the cytoplasm of mammalian cells. We unravel the spatial cycles of solubilisation, trapping on perinuclear membrane compartments and vesicular transport that counter entropic equilibration to endomembranes for maintaining the enrichment and activity of Src family protein tyrosine kinases at the plasma membrane. The solubilising factor UNC119 sequesters myristoylated Src family protein tyrosine kinases from the cytoplasm, enhancing their diffusion to effectively release Src family protein tyrosine kinases on the recycling endosome by localised Arl2/3 activity...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28724771/intracellular-colocalization-of-influenza-viral-rna-and-rab11a-is-dependent-upon-microtubule-filaments
#14
Eric Nturibi, Amar R Bhagwat, Stefanie Coburn, Mike M Myerburg, Seema S Lakdawala
Influenza A virus (IAV) consists of eight viral RNA (vRNA) segments that are replicated in the host cell nucleus and transported to the plasma membrane for packaging into progeny virions. We have previously proposed a model where sub-complexes of vRNA export from the nucleus and assemble en route to the plasma membrane. However, the role of host cytoskeletal proteins in the cytoplasmic assembly of IAV vRNA segments remains unknown. Previous studies have suggested that IAV vRNA segments transport via Rab11A-containing recycling endosomes (RE) and use both microtubules (MT) and actin...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#15
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724630/altered-met-receptor-phosphorylation-and-lrp1-mediated-uptake-in-cells-lacking-carbohydrate-dependent-lysosomal-targeting
#16
Megan Aarnio-Peterson, Peng Zhao, Seok-Ho Yu, Courtney Christian, Heather Flanagan-Steet, Lance Wells, Richard Steet
Acid hydrolases utilize a carbohydrate-dependent mechanism for lysosomal targeting. These hydrolases acquire a mannose 6-phosphate tag by the action of the GlcNAc-1-phosphotransferase enzyme, allowing them to bind receptors and traffic to endosomes. Loss of GlcNAc-1-phosphotransferase results in hydrolase hypersecretion and profound lysosomal storage. Little, however, is known about how these cellular phenotypes affect the trafficking, activity and localization of surface glycoproteins. To address this question, we profiled the abundance of surface glycoproteins in WT and CRISPR-mediated GNPTAB-/- HeLa cells and identified changes in numerous glycoproteins including the uptake receptor LRP1 and multiple receptor tyrosine kinases...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28722651/ephrin-a-epha-specific-co-adaptation-as-a-novel-mechanism-in-topographic-axon-guidance
#17
Felix Fiederling, Markus Weschenfelder, Martin Fritz, Anne von Philipsborn, Martin Bastmeyer, Franco Weth
Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28714518/regulation-of-tubular-recycling-endosome-biogenesis-by-the-p53-micall1-pathway
#18
Yukie Takahashi, Chizu Tanikawa, Takafumi Miyamoto, Makoto Hirata, Guanxiong Wang, Koji Ueda, Tsunehiko Komatsu, Koichi Matsuda
p53, one of the most frequently mutated genes in colon cancer, suppresses cancer development through transactivation of its targets. Herein, we conducted a comprehensive analysis of the p53 downstream pathway in colorectal cancer by using multi-omics analysis. Mass spectrometric analysis of HCT116 p53+/+ and HCT116 p53-/- cells treated with adriamycin identified 124 proteins increased by DNA damage in a p53-dependent manner. Further screening using a cDNA microarray and the TCGA database revealed MICALL1 as a novel p53 target, and we identified functional p53 binding motifs located approximately 3000 base pairs upstream of the MICALL1 gene...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28713240/the-coordinated-action-of-calcineurin-and-cathepsin-d-protects-against-%C3%AE-synuclein-toxicity
#19
Andreas Aufschnaiter, Lukas Habernig, Verena Kohler, Jutta Diessl, Didac Carmona-Gutierrez, Tobias Eisenberg, Walter Keller, Sabrina Büttner
The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca(2+) homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28705836/essential-and-selective-role-of-snx12-in-transport-of-endocytic-and-retrograde-cargo
#20
Amulya Priya, Jini Sugatha, Sameena Parveen, Sandra Lacas-Gervais, Prateek Raj, Jérôme Gilleron, Sunando Datta
The endosomal protein-sorting machineries play vital roles in diverse physiologically important cellular processes. Much of the core membrane-sorting apparatus is conserved in evolution, such as retromer, which is involved in the recycling of a diverse set of cargoes via the retrograde trafficking route. Here, in an RNAi-based loss-of-function study, we identified that suppression of SNX12 leads to a severe blockage in CIM6PR (also known as IGF2R) transport and alters the morphology of the endocytic compartments...
August 15, 2017: Journal of Cell Science
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