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Endosomal trafficking

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https://www.readbyqxmd.com/read/28345032/agrobacterium-delivers-vire2-protein-into-host-cells-via-clathrin-mediated-endocytosis
#1
Xiaoyang Li, Shen Q Pan
Agrobacterium tumefaciens can cause crown gall tumors on a wide range of host plants. As a natural genetic engineer, the bacterium can transfer both single-stranded DNA (ssDNA) [transferred DNA (T-DNA)] molecules and bacterial virulence proteins into various recipient cells. Among Agrobacterium-delivered proteins, VirE2 is an ssDNA binding protein that is involved in various steps of the transformation process. However, it is not clear how plant cells receive the T-DNA or protein molecules. Using a split-green fluorescent protein approach, we monitored the VirE2 delivery process inside plant cells in real time...
March 2017: Science Advances
https://www.readbyqxmd.com/read/28337939/bidirectional-apical-basal-traffic-of-the-cation-independent-mannose-6-phosphate-receptor-in-brain-endothelial-cells
#2
Piotr Siupka, Maria Ns Hersom, Karin Lykke-Hartmann, Kasper B Johnsen, Louiza B Thomsen, Thomas L Andresen, Torben Moos, N Joan Abbott, Birger Brodin, Morten S Nielsen
Brain capillary endothelium mediates the exchange of nutrients between blood and brain parenchyma. This barrier function of the brain capillaries also limits passage of pharmaceuticals from blood to brain, which hinders treatment of several neurological disorders. Receptor-mediated transport has been suggested as a potential pharmaceutical delivery route across the brain endothelium, e.g. reports have shown that the transferrin receptor (TfR) facilitates transcytosis of TfR antibodies, but it is not known whether this recycling receptor itself traffics from apical to basal membrane in the process...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28336235/tyrosine-phosphorylation-of-rab7-by-src-kinase
#3
Xiaosi Lin, Jiaming Zhang, Lingqiu Chen, Yongjun Chen, Xiaohui Xu, Wanjin Hong, Tuanlao Wang
The small molecular weight GTPase Rab7 is a key regulator for late endosomal/lysosomal membrane trafficking, it was known that Rab7 is phosphorylated, but the corresponding kinase and the functional regulation of Rab7 phosphorylation remain unclear. We provide evidence here that Rab7 is a substrate of Src kinase, and is tyrosine-phosphorylated by Src, withY183 residue of Rab7 being the optimal phosphorylation site for Src. Further investigations demonstrated that the tyrosine phosphorylation of Rab7 depends on the guanine nucleotide binding activity of Rab7 and the activity of Src kinase...
March 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28334785/amino-acid-substitution-equivalent-to-human-chorea-acanthocytosis-i2771r-in-yeast-vps13-protein-affects-its-binding-to-phosphatidylinositol-3-phosphate
#4
Weronika Rzepnikowska, Krzysztof Flis, Joanna Kaminska, Marcin Grynberg, Agnieszka Urbanek, Kathryn R Ayscough, Teresa Zoladek
The rare human disorder chorea-acanthocytosis (ChAc) is caused by mutations in hVPS13A gene. The hVps13A protein interacts with actin and regulates the level of phosphatidylinositol 4-phosphate (PI4P) in the membranes of neuronal cells. Yeast Vps13 is involved in vacuolar protein transport and, like hVps13A, participates in PI4P metabolism. Vps13 proteins are conserved in eukaryotes, but their molecular function remains unknown. One of the mutations found in ChAc patients causes amino acids substitution I2771R which affects the localization of hVps13A in skeletal muscles...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333714/novel-regulators-of-plasma-lipid-levels
#5
Natalia Loaiza, Federico Oldoni, Jan A Kuivenhoven
PURPOSE OF REVIEW: To highlight very recent studies identifying novel regulatory molecules and mechanisms in plasma lipid metabolism. RECENT FINDINGS: Two novel regulatory mechanisms of LDL receptor (LDLR) intracellular trafficking have been described. The "COMMD/CCDC22/CCDC93" and "Wiskott-Aldrich syndrome protein and SCAR homologue" complexes were found to be involved in LDLR endosomal sorting and recycling, whereas the GRP94 was shown to protect LDLR from early degradation within the hepatocyte secretory pathway...
March 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28331092/monkeypox-virus-host-factor-screen-in-haploid-cells-identifies-essential-role-of-garp-complex-in-extracellular-virus-formation
#6
Susan Realegeno, Andreas S Puschnik, Amrita Kumar, Cynthia Goldsmith, Jillybeth Burgado, Suryaprakash Sambhara, Victoria A Olson, Darin Carroll, Inger Damon, Tetsuya Hirata, Taroh Kinoshita, Jan E Carette, Panayampalli Subbian Satheshkumar
Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis and glycosylphosphatidylinositol (GPI) - anchor biosynthesis...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28324111/arap1-deficiency-causes-photoreceptor-degeneration-in-mice
#7
Ala Moshiri, Devin Humpal, Brian C Leonard, Denise M Imai, Addy Tham, Lynette Bower, Dave Clary, Thomas M Glaser, K C Kent Lloyd, Christopher J Murphy
Purpose: Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the control of GTPase-activating proteins (GAPs). Arap1 is an Arf-directed GAP that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome, but the diversity of its functions is incompletely understood. The aim of this study was to determine the role of Arap1 in the mammalian retina. Methods: Genetically engineered Arap1 knockout mice were screened for ocular abnormalities in the National Institutes of Health Knockout Mouse Production and Phenotyping (KOMP2) Project...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28320834/early-intracellular-trafficking-of-granulibacter-bethesdensis-in-human-macrophages
#8
Jessica Chu, Margery G Smelkinson, David W Dorward, Kol A Zarember, John I Gallin
Granulibacter bethesdensis is a Gram-negative bacterium that infects patients with Chronic Granulomatous Disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the phagocyte nicotinamide adenine dinucleotide phosphate oxidase. Previous studies have shown that NOX2 is essential for killing of G. bethesdensis by neutrophils and monocytes and that bacteriostatic activity of monocyte derived macrophages (MDM) requires NOX2 and IFNγ-pretreatment. To determine if G. bethesdensis evades phagolysosomal killing, a host defense pathway intact in both normal and CGD MDM, or occupies a distinct intracellular niche in CGD MDM, we assessed the trafficking patterns of this organism...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28319098/irap-endosomes-restrict-tlr9-activation-and-signaling
#9
Joel Babdor, Delphyne Descamps, Aimé Cézaire Adiko, Mira Tohmé, Sophia Maschalidi, Irini Evnouchidou, Luiz Ricardo Vasconcellos, Mariacristina De Luca, Francois-Xavier Mauvais, Meriem Garfa-Traore, Melanie M Brinkmann, Michel Chignard, Bénédicte Manoury, Loredana Saveanu
The retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP(+) endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP(+) endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection...
March 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28318354/hs1bp3-inhibits-autophagy-by-regulation-of-pld1
#10
Kristiane Søreng, Helene Knævelsrud, Petter Holland, Anne Simonsen
Macroautophagy/autophagy is a membrane trafficking and intracellular degradation process involving the formation of double-membrane autophagosomes and their ultimate fusion with lysosomes. Much is yet to be learned about the regulation of this process, especially at the level of the membranes and lipids involved. We have recently found that the PX domain protein HS1BP3 (HCLS1 binding protein 3) is a negative regulator of autophagosome formation. HS1BP3 depletion increases the formation of LC3-positive autophagosomes both in human cells and zebrafish...
February 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28317021/the-bloc-1-subunit-pallidin-facilitates-activity-dependent-synaptic-vesicle-recycling
#11
Xun Chen, Wenpei Ma, Shixing Zhang, Jeremy Paluch, Wanlin Guo, Dion K Dickman
Membrane trafficking pathways must be exquisitely coordinated at synaptic terminals to maintain functionality, particularly during conditions of high activity. We have generated null mutations in the Drosophila homolog of pallidin, a central subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), to determine its role in synaptic development and physiology. We find that Pallidin localizes to presynaptic microtubules and cytoskeletal structures, and that the stability of Pallidin protein is highly dependent on the BLOC-1 components Dysbindin and Blos1...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28301372/news-on-the-molecular-regulation-and-function-of-hepatic-low-density-lipoprotein-receptor-and-ldlr-related-protein-1
#12
Bart van de Sluis, Melinde Wijers, Joachim Herz
PURPOSE OF REVIEW: Clearing of atherogenic lipoprotein particles by the liver requires hepatic low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1). This review highlights recent studies that have expanded our understanding of the molecular regulation and metabolic functions of LDLR and LRP1 in the liver. RECENT FINDINGS: Various proteins orchestrate the intracellular trafficking of LDLR and LRP1. After internalization, the receptors are redirected via recycling endosomes to the cell surface...
March 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28300561/nucleolin-is-a-nuclear-target-of-heparan-sulfate-derived-from-glypican-1
#13
Fang Cheng, Mattias Belting, Lars-Åke Fransson, Katrin Mani
The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells...
March 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28299779/the-related-neuronal-endosomal-proteins-neep21-nsg1-and-p19-nsg2-have-divergent-expression-profiles-in-vivo
#14
Kelly Barford, Chan Choo Yap, Noelle D Dwyer, Bettina Winckler
Endosomal maturation and transport constitutes a complex trafficking system present in all cell types. Neurons have adapted their endosomal system to meet their unique and complex needs. These adaptations include repurposing existing proteins to diversify endocytosis and trafficking, as well as preferential expression of certain regulators more highly in neurons than other cell types. These neuronal regulators include the family of Neuron-Specific Gene family members (Nsg), NEEP21 (Nsg1), and P19 (Nsg2). NEEP21/Nsg1 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and β-APP...
March 15, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28296950/cellular-and-molecular-defects-in-a-patient-with-hermansky-pudlak-syndrome-type-5
#15
Joshi Stephen, Tadafumi Yokoyama, Nathanial J Tolman, Kevin J O'Brien, Elena-Raluca Nicoli, Brian P Brooks, Laryssa Huryn, Steven A Titus, David R Adams, Dong Chen, William A Gahl, Bernadette R Gochuico, May Christine V Malicdan
Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of genetic disorders typically manifesting with tyrosinase-positive oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis, in some subtypes. Most HPS subtypes are associated with defects in Biogenesis of Lysosome-related Organelle Complexes (BLOCs), which are groups of proteins that function together in the formation and/or trafficking of lysosomal-related endosomal compartments. BLOC-2, for example, consists of the proteins HPS3, HPS5, and HPS6...
2017: PloS One
https://www.readbyqxmd.com/read/28293541/high-content-imaging-reveals-expansion-of-the-endosomal-compartment-during-coxiella-burnetii-parasitophorous-vacuole-maturation
#16
Charles L Larson, Robert A Heinzen
Coxiella burnetii is an obligate intracellular pathogen and the causative agent of human Q fever. Replication of the bacterium within a large parasitophorous vacuole (PV) resembling a host phagolysosome is required for pathogenesis. PV biogenesis is a pathogen driven process that requires engagement of several host cell vesicular trafficking pathways to acquire vacuole components. The goal of this study was to determine if infection by C. burnetii modulates endolysosomal flux to potentially benefit PV formation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28293032/planar-cell-polarity-in-development-and-disease
#17
REVIEW
Mitchell T Butler, John B Wallingford
Planar cell polarity (PCP) is an essential feature of animal tissues, whereby distinct polarity is established within the plane of a cell sheet. Tissue-wide establishment of PCP is driven by multiple global cues, including gradients of gene expression, gradients of secreted WNT ligands and anisotropic tissue strain. These cues guide the dynamic, subcellular enrichment of PCP proteins, which can self-assemble into mutually exclusive complexes at opposite sides of a cell. Endocytosis, endosomal trafficking and degradation dynamics of PCP components further regulate planar tissue patterning...
March 15, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28283744/serial-block-face-scanning-electron-microscopy-applied-to-study-the-trafficking-of-8d3-coated-gold-nanoparticles-at-the-blood-brain-barrier
#18
Itsaso Cabezón, Elisabet Augé, Manel Bosch, Alison J Beckett, Ian A Prior, Carme Pelegrí, Jordi Vilaplana
Due to the physical and physiological properties of the blood-brain barrier (BBB), the transport of neurotherapeutics from blood to brain is still a pharmaceutical challenge. We previously conducted a series of experiments to explore the potential of the anti-transferrin receptor 8D3 monoclonal antibody (mAb) to transport neurotherapeutics across the BBB. In that study, gold nanoparticles (AuNPs) were coated with the 8D3 antibody and administered intravenously to mice. Transmission electron microscopy was used and a two-dimensional (2D) image analysis was performed to detect the AuNPs in the brain capillary endothelial cells (BCECs) and brain parenchyma...
March 10, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28274796/dual-functional-lipomet-mediates-envelope-type-nanoparticles-to-combinational-oncogene-silencing-and-tumor-growth-inhibition
#19
Kai Shi, Yi Zhao, Lei Miao, Andrew Satterlee, Matthew Haynes, Cong Luo, Sara Musetti, Leaf Huang
The success of small interfering RNA (siRNA)-mediated gene silencing for cancer therapy is still limited because of its instability and poor intracellular internalization. Traditional cationic carriers cannot adequately meet the need for clinical application of siRNA. We herein report a dual-functional liposome containing a cholesterol derivative of metformin, i.e., LipoMET, which takes advantage of the fusogenic activity as well as intrinsic tumor apoptosis inducing ability of biguanide moiety to achieve a combinational anti-oncogenic effect...
March 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28273919/differential-modulation-of-the-cellular-and-humoral-immune-responses-in-drosophila-is-mediated-by-the-endosomal-arf1-asrij-axis
#20
Rohan J Khadilkar, Arindam Ray, D R Chetan, Arghyashree RoyChowdhury Sinha, Srivathsa S Magadi, Vani Kulkarni, Maneesha S Inamdar
How multicellular organisms maintain immune homeostasis across various organs and cell types is an outstanding question in immune biology and cell signaling. In Drosophila, blood cells (hemocytes) respond to local and systemic cues to mount an immune response. While endosomal regulation of Drosophila hematopoiesis is reported, the role of endosomal proteins in cellular and humoral immunity is not well-studied. Here we demonstrate a functional role for endosomal proteins in immune homeostasis. We show that the ubiquitous trafficking protein ADP Ribosylation Factor 1 (ARF1) and the hemocyte-specific endosomal regulator Asrij differentially regulate humoral immunity...
December 2017: Scientific Reports
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