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Endosomal trafficking

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https://www.readbyqxmd.com/read/28716909/internalized-cd44s-splice-isoform-attenuates-egfr-degradation-by-targeting-rab7a
#1
Wei Wang, Honghong Zhang, Sali Liu, Chung Kwon Kim, Yilin Xu, Lisa A Hurley, Ryo Nishikawa, Motoo Nagane, Bo Hu, Alexander H Stegh, Shi-Yuan Cheng, Chonghui Cheng
CD44 has been postulated as a cell surface coreceptor for augmenting receptor tyrosine kinase (RTK) signaling. However, how exactly CD44 triggers RTK-dependent signaling remained largely unclear. Here we report an unexpected mechanism by which the CD44s splice isoform is internalized into endosomes to attenuate EGFR degradation. We identify a CD44s-interacting small GTPase, Rab7A, and show that CD44s inhibits Rab7A-mediated EGFR trafficking to lysosomes and subsequent degradation. Importantly, CD44s levels correlate with EGFR signature and predict poor prognosis in glioblastomas...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28712489/plant-made-virus-like-particles-bearing-influenza-hemagglutinin-ha-recapitulate-early-interactions-of-native-influenza-virions-with-human-monocytes-macrophages
#2
Alexander I Makarkov, Sabrina Chierzi, Stéphane Pillet, Keith K Murai, Nathalie Landry, Brian J Ward
INTRODUCTION: Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC)...
July 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28710431/hiv-1-enhances-mtorc1-activity-and-repositions-lysosomes-to-the-periphery-by-co-opting-rag-gtpases
#3
Alessandro Cinti, Valerie Le Sage, Miroslav P Milev, Fernando Valiente-Echeverría, Christina Crossie, Marie-Joelle Miron, Nelly Panté, Martin Olivier, Andrew J Mouland
HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endosome/lysosome (LEL) trafficking in stressful conditions. First, HIV-1 enhances the activity of the master regulator of protein synthesis, the mammalian target of rapamycin (mTOR). Second, the virus commandeers mTOR-associated late endosome/lysosome (LEL) trafficking and counteracts metabolic and environmental stress-induced intracellular repositioning of LEL...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705836/essential-and-selective-role-of-snx12-in-transport-of-endocytic-and-retrograde-cargo
#4
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 are conserved in evolution, such as retromer, involved in the recycling of a diverse set of cargoes via retrograde trafficking route. Here, using a RNAi based loss of function study, we identified that SNX12 when suppressed, leads to severe blockage in CIM6PR transport and alters the morphology of the endocytic compartments. We demonstrate that SNX12 is involved in the early phase of CIM6PR transport and mediates receptor recycling upstream of the other well established SNX components of retromer...
July 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28705375/regulation-of-expression-and-trafficking-of-perforin-2-by-lps-and-tnf-%C3%AE
#5
Peng Xiong, Motoaki Shiratsuchi, Takamitsu Matsushima, Jiyuan Liao, Emi Tanaka, Yasuhiro Nakashima, Ryoichi Takayanagi, Yoshihiro Ogawa
Perforin-2 is constitutively expressed in macrophages that are required for bacterial control. In this study, we found that perforin-2 is expressed in human macrophages with two isoforms: full-length perforin-2a and a splice variant, perforin-2b. Two isoforms show different subcellular distributions. Perforin-2a was predominantly localized to the membrane of endosome-like vesicles by a C-terminal transmembrane domain. In contrast, the short isoform perforin-2b lacking the transmembrane domain failed to localize to the membrane of vesicles...
July 8, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28704415/c-elegans-sma-10-regulates-bmp-receptor-trafficking
#6
Ryan J Gleason, Mehul Vora, Ying Li, Nanci S Kane, Kelvin Liao, Richard W Padgett
Signal transduction of the conserved transforming growth factor-β (TGFβ) family signaling pathway functions through two distinct serine/threonine transmembrane receptors, the type I and type II receptors. Endocytosis orchestrates the assembly of signaling complexes by coordinating the entry of receptors with their downstream signaling mediators. Recently, we showed that the C. elegans type I bone morphogenetic protein (BMP) receptor SMA-6, part of the TGFβ family, is recycled through the retromer complex while the type II receptor, DAF-4 is recycled in a retromer-independent, ARF-6 dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/28697973/traffic-jam-hypothesis-relationship-between-endocytic-dysfunction-and-alzheimer-s-disease
#7
REVIEW
Nobuyuki Kimura, Katsuhiko Yanagisawa
Membrane trafficking pathways, like the endocytic pathway, carry out fundamental cellular processes that are essential for normal functioning. One such process is regulation of cell surface receptor signaling. A growing body of evidence suggests that β-amyloid protein (Aβ) plays a key role in Alzheimer's disease (AD) pathogenesis. Cleavage of Aβ from its precursor, β-amyloid precursor protein (APP), occurs through the endocytic pathway in neuronal cells. In early-stage AD, intraneuronal accumulation of abnormally enlarged endosomes is common, indicating that endosome trafficking is disrupted...
July 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28696297/mtorc1-activates-srebp-2-by-suppressing-cholesterol-trafficking-to-lysosomes-in-mammalian-cells
#8
Walaa Eid, Kristin Dauner, Kevin C Courtney, AnneMarie Gagnon, Robin J Parks, Alexander Sorisky, Xiaohui Zha
mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing cholesterol delivery to the ER...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28696251/endothelin-1-stimulates-vasoconstriction-through-rab11a-serine-177-phosphorylation
#9
Xue Zhai, Marie D Leo, Jonathan H Jaggar
Rationale: Large-conductance calcium (Ca(2+))-activated potassium channels (BK) are composed of pore-forming BKα and auxiliary β1 subunits in arterial smooth muscle cells (myocytes). Vasoconstrictors, including endothelin-1 (ET-1), inhibit myocyte BK channels, leading to contraction, but mechanisms involved are unclear. Recent evidence indicates that BKα is primarily plasma membrane-localized, whereas the cellular location of β1 can be rapidly altered by Rab11A-positive recycling endosomes. Whether vasoconstrictors regulate the multi-subunit composition of surface BK channels to stimulate contraction is unclear...
July 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28688576/vamp8-mediated-nox2-recruitment-to-endosomes-is-necessary-for-antigen-release
#10
Ilse Dingjan, Laurent M Paardekooper, Daniëlle R J Verboogen, Gabriele Fischer von Mollard, Martin Ter Beest, Geert van den Bogaart
Cross-presentation of foreign antigen in major histocompatibility complex (MHC) class I by dendritic cells (DCs) requires activation of the NADPH-oxidase NOX2 complex. We recently showed that NOX2 is recruited to phagosomes by the SNARE protein VAMP8 where NOX2-produced reactive oxygen species (ROS) cause lipid oxidation and membrane disruption, promoting antigen translocation into the cytosol for cross-presentation. In this study, we extend these findings by showing that VAMP8 is also involved in NOX2 trafficking to endosomes...
June 23, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28687362/the-unexpected-function-of-a-highly-conserved-yxx%C3%AE-motif-in-hcv-core-protein
#11
Eirini Karamichali, Elisavet Serti, Aikaterini Gianneli, Aikaterini Papaefthymiou, Athanassios Kakkanas, Pelagia Foka, Alexandros Seremetakis, Konstantina Katsarou, Ioannis P Trougakos, Urania Georgopoulou
Hepatitis C virus (HCV) is an RNA positive strand virus, member of the Flaviviridae family. The HCV viral particle is composed of a capsid containing the genome, surrounded by an endoplasmic reticulum (ER)-derived lipid bilayer where E1 and E2 are assembled as heterodimers. However, different forms of viral particles have been identified in the serum of HCV-infected patients, including non-enveloped particles. Previous reports have demonstrated that HCV non-enveloped capsid-like particles (HCVne) can be generated by HCV core protein sequence...
July 4, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28685959/targeting-cholesterol-transport-in-circulating-melanoma-cells-to-inhibit-metastasis
#12
Yu-Chi Chen, Raghavendra Gowda, Raymond K Newswanger, Patrick Leibich, Barry Fell, Gerson Rosenberg, Gavin P Robertson
Despite recent break throughs in targeted- and immune-based therapies, rapid development of drug resistance remains a hurdle for the long-term treatment of melanoma patients. Targeting metastatically spreading circulating tumor cells (CTCs) may provide an additional approach to manage melanoma. This study investigates whether targeting cholesterol transport in melanoma CTCs can retard metastasis development. Nanolipolee-007, the liposomal form of leelamine, reduced melanoma metastasis in both a novel in vitro flow system mimicking the circulating system and in experimental as well as spontaneous animal metastasis models, irrespective of the BRAF mutational status of the CTCs...
July 7, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28684042/signal-dependent-transport-of-a-membrane-cargo-from-early-endosomes-to-recycling-endosomes
#13
Ismail S Mahmoud, Jade Louber, Steve K Dower, Anne M Verhagen, Paul A Gleeson
Many membrane cargoes undergo endocytosis and intracellular recycling to the plasma membrane via the early endosomes and the recycling endosomes. However whether specific sorting signals are required for transport from early endosomes to recycling endosomes is not known and the current view is that transport to the recycling endosomes is by a passive default process. Here we show that the cytoplasmic tail of the neonatal Fc receptor (FcRn) contains discrete signals for endocytosis and for sorting to the recycling endosomes...
June 17, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28682417/impact-of-a-mechanical-shear-stress-on-intracellular-trafficking
#14
Kelly Aubertin, Julien Tailleur, Claire Wilhelm, François Gallet
Intracellular trafficking mainly takes place along the microtubules, and its efficiency depends on the local architecture and organization of the cytoskeletal network. In this work, the cytoplasm of stem cells is subjected to mechanical vortexing at a frequency of up to 1 Hz, by using magnetic chains of endosomes embedded in the cell body, in order to locally perturb the network structure. The consequences are evaluated on the directionality and processivity of the spontaneous motion of endosomes. When the same chains are used both to shear the cell medium and to probe the intracellular traffic, a substantial decrease in transport efficiency is detected after applying the mechanical shear...
July 6, 2017: Soft Matter
https://www.readbyqxmd.com/read/28679634/sec61-blockade-by-mycolactone-inhibits-antigen-cross-presentation-independently-of-endosome-to-cytosol-export
#15
Jeff E Grotzke, Patrycja Kozik, Jean-David Morel, Francis Impens, Natalia Pietrosemoli, Peter Cresswell, Sebastian Amigorena, Caroline Demangel
Although antigen cross-presentation in dendritic cells (DCs) is critical to the initiation of most cytotoxic immune responses, the intracellular mechanisms and traffic pathways involved are still unclear. One of the most critical steps in this process, the export of internalized antigen to the cytosol, has been suggested to be mediated by Sec61. Sec61 is the channel that translocates signal peptide-bearing nascent polypeptides into the endoplasmic reticulum (ER), and it was also proposed to mediate protein retrotranslocation during ER-associated degradation (a process called ERAD)...
July 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28678789/egfr-controls-drosophila-tracheal-tube-elongation-by-intracellular-trafficking-regulation
#16
Ivette Olivares-Castiñeira, Marta Llimargas
Development is governed by a few conserved signalling pathways. Amongst them, the EGFR pathway is used reiteratively for organ and tissue formation, and when dysregulated can lead to cancer and metastasis. Given its relevance, identifying its downstream molecular machinery and understanding how it instructs cellular changes is crucial. Here we approach this issue in the respiratory system of Drosophila. We identify a new role for EGFR restricting the elongation of the tracheal Dorsal Trunk. We find that EGFR regulates the apical determinant Crb and the extracellular matrix regulator Serp, two factors previously known to control tube length...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28675177/norrin-induced-frizzled4-endocytosis-and-endo-lysosomal-trafficking-control-retinal-angiogenesis-and-barrier-function
#17
Chi Zhang, Maria B Lai, Lavan Khandan, Lindsey A Lee, Zhe Chen, Harald J Junge
Angiogenesis and blood-brain barrier formation are required for normal central nervous system (CNS) function. Both processes are controlled by Wnt or Norrin (NDP) ligands, Frizzled (FZD) receptors, and β-catenin-dependent signalling in vascular endothelial cells. In the retina, FZD4 and the ligand NDP are critical mediators of signalling and are mutated in familial exudative vitreoretinopathy. Here, we report that NDP is a potent trigger of FZD4 ubiquitination and induces internalization of the NDP receptor complex into the endo-lysosomal compartment...
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28672171/host-determinants-of-adeno-associated-viral-vector-entry
#18
REVIEW
Sirika Pillay, Jan E Carette
Viral vectors based on adeno-associated virus (AAV) are leading candidates for therapeutic gene delivery. Understanding rate-limiting steps in the entry of AAV vectors may be used in a rational approach to improve efficiency and specificity of transduction. This review describes our current understanding of AAV entry, a key step during infection. We discuss the identity and functions of AAV receptors and attachment factors, including the recently discovered multi-serotype receptor AAVR. We further provide an overview of other host factors that act during the trafficking stage of AAV vector transduction...
June 30, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28666573/mlkl-the-protein-that-mediates-necroptosis-also-regulates-endosomal-trafficking-and-extracellular-vesicle-generation
#19
Seongmin Yoon, Andrew Kovalenko, Konstantin Bogdanov, David Wallach
Activation of the pseudokinase mixed lineage kinase domain-like (MLKL) upon its phosphorylation by the protein kinase RIPK3 triggers necroptosis, a form of programmed cell death in which rupture of cellular membranes yields release of intracellular components. We report that MLKL also associated with endosomes and controlled the transport of endocytosed proteins, thereby enhancing degradation of receptors and ligands, modulating their induced signaling and facilitating the generation of extracellular vesicles...
June 22, 2017: Immunity
https://www.readbyqxmd.com/read/28659475/a-small-viral-ppxy-peptide-motif-to-control-antiviral-autophagy
#20
Charlotte Montespan, Christopher M Wiethoff, Harald Wodrich
Autophagy is an essential metabolic program also used for clearing intracellular pathogens. This mechanism, also termed selective autophagy, is well characterised for invasive bacteria but remains poorly documented for viral infections. Here we highlight our recent work showing that endosomolytic adenoviruses trigger autophagy when entering cells. Our study revealed how adenoviruses exploit a capsid-associated small PPxY peptide motif to manipulate the autophagic machinery to prevent autophagic degradation and to promote endosomal escape and nuclear trafficking...
June 28, 2017: Journal of Virology
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