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Endocytic trafficking

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https://www.readbyqxmd.com/read/29031909/the-retromer-subunit-vps26-mediates-notch-signaling-during-drosophila-oogenesis
#1
Rebecca Starble, Nancy J Pokrywka
During endocytosis, molecules are internalized by the cell through the invagination of the plasma membrane. Endocytosis is required for proper cell function and for normal development in Drosophila. One component of the endocytic pathway is the retromer complex, which recycles transmembrane proteins to other parts of the cell such as the plasma membrane and the trans-Golgi network. Previous studies have shown that mutations to the retromer complex result in developmental defects in Drosophila. In humans, retromer dysfunction has been implicated in Alzheimer's and Parkinson's disease, but little is known about the role of the retromer complex in Drosophila oogenesis...
October 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/29028801/docrl-maintains-immune-cell-quiescence-by-regulating-endosomal-traffic
#2
Steven J Del Signore, Sarah A Biber, Katherine S Lehmann, Stephanie R Heimler, Benjamin H Rosenfeld, Tania L Eskin, Sean T Sweeney, Avital A Rodal
Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system...
October 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29028540/endo-lysosomal-dysfunction-a-converging-mechanism-in-neurodegenerative-diseases
#3
REVIEW
Chao Wang, Maria A Telpoukhovskaia, Ben A Bahr, Xu Chen, Li Gan
Endo-lysosomal pathways are essential in maintaining protein homeostasis in the cell. Numerous genes in the endo-lysosomal pathways have been found to associate with neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementia (FTD). Mutations of these genes lead to dysfunction in multiple steps of the endo-lysosomal network: autophagy, endocytic trafficking and lysosomal degradation, resulting in accumulation of pathogenic proteins. Although the exact pathogenic mechanism varies for different disease-associated genes, dysfunction of the endo-lysosomal pathways represents a converging mechanism shared by these diseases...
October 10, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29018878/investigating-internalization-and-intracellular-trafficking-of-gpcrs-new-techniques-and-real-time-experimental-approaches
#4
Simon R Foster, Hans Bräuner-Osborne
The ability to regulate the interaction between cells and their extracellular environment is essential for the maintenance of appropriate physiological function. For G protein-coupled receptors (GPCRs), this regulation occurs through multiple mechanisms that provide spatial and temporal control for signal transduction. One of the major mechanisms for GPCR regulation involves their endocytic trafficking, which serves to internalize the receptors from the plasma membrane and thereby attenuate G protein-dependent signaling...
October 11, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29016942/ben3-big2-arf-gef-is-involved-in-brefeldin-a-sensitive-trafficking-at-the-trans-golgi-network-early-endosome-in-arabidopsis-thaliana
#5
Saeko Kitakura, Maciek Adamowski, Yuki Matsuura, Luca Santuari, Hirotaka Kouno, Kohei Arima, Christian S Hardtke, Jirí Friml, Tatsuo Kakimoto, Hirokazu Tanaka
Membrane traffic at the trans-Golgi network (TGN) is crucial for correctly distributing various membrane proteins to their destination. Polarly localized auxin efflux proteins, including PIN-FORMED1 (PIN1), are dynamically transported between the endosomes and the plasma membrane (PM) in the plant cells. The intracellular trafficking of PIN1 protein is sensitive to a fungal toxin brefeldin A (BFA), which is known to inhibit guanine-nucleotide exchange factors for ADP ribosylation factors (ARF GEFs) such as GNOM...
August 21, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28993644/membrane-trafficking-modulation-during-entamoeba-encystation
#6
Emily Herman, Maria A Siegesmund, Michael J Bottery, Ronny van Aerle, Maulood Mohammed Shather, Elisabet Caler, Joel B Dacks, Mark van der Giezen
Entamoeba histolytica is an intestinal parasite that infects 50-100 million people and causes up to 55,000 deaths annually. The transmissive form of E. histolytica is the cyst, with a single infected individual passing up to 45 million cysts per day, making cyst production an attractive target for infection control. Lectins and chitin are secreted to form the cyst wall, although little is known about the underlying membrane trafficking processes supporting encystation. As E. histolytica does not readily form cysts in vitro, we assessed membrane trafficking gene expression during encystation in the closely related model Entamoeba invadens...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28979836/a-new-role-for-human-dyskerin-in-vesicular-trafficking
#7
Nunzia Di Maio, Rosario Vicidomini, Alberto Angrisani, Valentina Belli, Maria Furia, Mimmo Turano
Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X-linked dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. To further investigate the wide range of dyskerin's biological roles, we set up stable cell lines able to trigger inducible protein knockdown and allow a detailed analysis of the cascade of events occurring within a short time frame. We report that dyskerin depletion quickly induces cytoskeleton remodeling and significant alterations in endocytic Ras-related protein Rab-5A/Rab11 trafficking...
October 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28976196/mitochondria-alkylation-and-cellular-trafficking-mapped-with-a-lipophilic-bodipy-acrolein-fluorogenic-probe
#8
Richard Lincoln, Lana E Greene, Wenzhou Zhang, Sheena Louisia, Gonzalo Cosa
Protein and DNA alkylation by endogenously produced electrophiles is associated with the pathogenesis of neurodegenerative diseases, to epigenetic alterations and to cell signaling and redox regulation. With the goal of visualizing, in real-time, the spatiotemporal response of the cell milieu to electrophiles, we have designed a fluorogenic BODIPY-acrolein probe, AcroB, that undergoes a >350-fold fluorescence intensity enhancement concomitant with protein adduct formation. AcroB enables a direct quantification of single post-translational modifications occurring on cellular proteins via recording fluorescence bursts in live-cell imaging studies...
October 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28974266/endophilin-a2-promotes-her2-internalization-and-sensitivity-to-trastuzumab-based-therapy-in-her2-positive-breast-cancers
#9
Tomas Baldassarre, Peter Truesdell, Andrew W Craig
BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is amplified and a clinical target in a subset of human breast cancers with high rates of metastasis. Targeted therapies involving the antibody trastuzumab and trastuzumab-emtansine (T-DM1) have greatly improved outcomes for HER2-positive (HER2+) breast cancer patients. However, resistance to these targeted therapies can develop and limit their efficacy. Here, we test the involvement of the endocytic adaptor protein endophilin A2 (Endo II) in HER2+ breast cancer models, and their responses to treatments with trastuzumab and T-DM1...
October 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28963439/neuroprotective-astrocyte-derived-insulin-insulin-like-growth-factor-1-stimulates-endocytic-processing-and-extracellular-release-of-neuron-bound-a%C3%AE-oligomers
#10
Jason Pitt, Kyle C Wilcox, Vanessa Tortelli, Luan Pereira Diniz, Maira S Oliveira, Cassandra Dobbins, Xiao-Wen Yu, Sathwik Nandamuri, Flávia C A Gomes, Nadia DiNunno, Kirsten L Viola, Fernanda G De Felice, Sergio T Ferreira, William L Klein
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AβOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aβ pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of AβOs. Here we employed physically separated neuron-astrocyte cocultures to investigate potential non-cell autonomous neuroprotective factors influencing AβO toxicity...
October 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28961039/clathrin-mediated-integrin-%C3%AE-iib%C3%AE-3-trafficking-controls-platelet-spreading
#11
Wen Gao, Panlai Shi, Xue Chen, Lin Zhang, Junling Liu, Xuemei Fan, Xinping Luo
Dynamic endocytic and exocytic trafficking of integrins is an important mechanism for cell migration, invasion, and cytokinesis. Endocytosis of integrin can be classified as clathrin dependent and clathrin independent manners. And rapid delivery of endocytic integrins back to the plasma membrane is key intracellular signals and is indispensable for cell movement. Integrin αIIbβ3 plays a critical role in thrombosis and hemostasis. Although previous studies have demonstrated that internalization of fibrinogen-bound αIIbβ3 may regulate platelet activation, the roles of endocytic and exocytic trafficking of integrin αIIbβ3 in platelet activation are unclear...
September 29, 2017: Platelets
https://www.readbyqxmd.com/read/28960957/in-vivo-neuroimaging-of-exosomes-using-gold-nanoparticles
#12
Oshra Betzer, Nisim Perets, Ariel Angel, Menachem Motiei, Tamar Sadan, Gal Yadid, Daniel Offen, Rachela Popovtzer
Exosomes are emerging as effective therapeutic tools for various pathologies. These extracellular vesicles can bypass biological barriers, including the blood-brain barrier, and can serve as powerful drug and gene therapy transporters. However, the progress of therapy development is impeded by several challenges, including insufficient data on exosome trafficking and biodistribution and the difficulty to image deep brain structures in vivo. Herein, we established a method for noninvasive in vivo neuroimaging and tracking of exosomes, based on glucose-coated gold nanoparticle (GNP) labeling and computed tomography imaging...
October 5, 2017: ACS Nano
https://www.readbyqxmd.com/read/28960134/differential-requirement-of-rab22a-for-the-recruitment-of-er-derived-proteins-to-phagosomes-and-endosomes-in-dendritic-cells
#13
Cristina Croce, Luis S Mayorga, Ignacio Cebrian
The recruitment of endoplasmic reticulum (ER) components to dendritic cell (DC) phagosomes and endosomes is a crucial event to achieve efficient cross-presentation of exogenous antigens. We have previously identified the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs. In this study we show that low expression of Rab22a does not prevent the normal delivery of ER-derived proteins to DC phagosomes. In contrast, the presence of these proteins was diminished in endosomes labelled with a fluid phase marker...
September 29, 2017: Small GTPases
https://www.readbyqxmd.com/read/28956766/porcine-hemagglutinating-encephalomyelitis-virus-enters-neuro-2a-cells-via-clathrin-mediated-endocytosis-in-a-rab5-cholesterol-and-ph-dependent-manner
#14
Zi Li, Kui Zhao, Yungang Lan, Xiaoling Lv, Shiyu Hu, Jiyu Guan, Huijun Lu, Jing Zhang, Junchao Shi, Yawen Yang, Deguang Song, Feng Gao, Wenqi He
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that invades the central nervous system (CNS) in piglets. Although important progress has been made towards understanding the biology of PHEV, many aspects of its life cycle remain obscure. Here, we dissected the molecular mechanism underlying cellular entry and intracellular trafficking of PHEV in mouse neuroblastoma (Neuro-2a) cells. We first performed a thin-section transmission electron microscopy (TEM) assay to characterize the kinetics of PHEV, and found that viral entry and transfer occur via membranous-coating-mediated endo-/exocytosis...
September 27, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28951554/endocytosis-and-lysosomal-degradation-of-glua2-3-ampars-in-response-to-oxygen-glucose-deprivation-in-hippocampal-but-not-cortical-neurons
#15
Zsombor Koszegi, Maria Fiuza, Jonathan G Hanley
Global cerebral ischemia results in oxygen and glucose deprivation (OGD) and consequent delayed cell death of vulnerable neurons, with hippocampal CA1 neurons more vulnerable than cortical neurons. Most AMPA receptors (AMPARs) are heteromeric complexes of subunits GluA1/GluA2 or GluA2/GluA3, and the presence of GluA2 renders AMPARs Ca(2+)-impermeable. In hippocampal CA1 neurons, OGD causes the synaptic expression of GluA2-lacking Ca(2+)-permeable AMPARs, contributing to toxic Ca(2+) influx. The loss of synaptic GluA2 is caused by rapid trafficking of GluA2-containing AMPARs from the cell surface, followed by a delayed reduction in GluA2 mRNA expression...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28946560/disruption-of-endocytic-trafficking-protein-rab7-impairs-invasiveness-of-cholangiocarcinoma-cells
#16
Nantana Suwandittakul, Onrapak Reamtong, Pattamaporn Molee, Santi Maneewatchararangsri, Maleerat Sutherat, Urai Chaisri, Sopit Wongkham, Poom Adisakwattana
BACKGROUND: Alterations and mutations of endo-lysosomal trafficking proteins have been associated with cancer progression. Identification and characterization of endo-lysosomal trafficking proteins in invasive cholangiocarcinoma (CCA) cells may benefit prognosis and drug design for CCA. OBJECTIVE: To identify and characterize endo-lysosomal trafficking proteins in invasive CCA. METHODS: A lysosomal-enriched fraction was isolated from a TNF-α induced invasive CCA cell line (KKU-100) and uninduced control cells and protein identification was performed with nano-LC MS/MS...
September 7, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28946017/par3-and-apkc-regulate-bace1-endosome-to-tgn-trafficking-through%C3%A2-pacs1
#17
Miao Sun, Huaye Zhang
The cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) is the rate-limiting step in beta amyloid generation during Alzheimer's disease (AD) pathogenesis. In AD brains, BACE1 is abnormally accumulated in endocytic compartments, where the acidic pH is optimal for its activity. However, mechanisms regulating the endosome-to-trans-Golgi network (TGN) retrieval of BACE1 remain unclear. Here, we show that partitioning defective 3 (Par3) facilitates BACE1 retrograde trafficking from endosomes to the TGN...
September 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28945820/anthrax-edema-toxin-disrupts-distinct-steps-in-rab11-dependent-junctional-transport
#18
Annabel Guichard, Prashant Jain, Mahtab Moayeri, Ruth Schwartz, Stephen Chin, Lin Zhu, Beatriz Cruz-Moreno, Janet Z Liu, Bernice Aguilar, Andrew Hollands, Stephen H Leppla, Victor Nizet, Ethan Bier
Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28944844/h2o2-induces-caveolin%C3%A2-1-degradation-and-impaired-mitochondrial-function-in-e11-podocytes
#19
Ya-Hui Chen, Wei-Wen Lin, Chin-San Liu, Shih-Li Su
Increased intercellular reactive oxygen species (ROS) levels are the major cause of podocyte injury with proteinuria. Caveolin‑1 (CAV‑1) is an essential protein component of caveolae. CAV‑1 participates in signal transduction and endocytic trafficking. Recent research has indicated that CAV‑1 regulates oxidative stress‑induced pathways. The present study used hydrogen peroxide (H2O2) at nontoxic concentrations to elevate the level of ROS in E11 podocytes. Treatment with 500 and 1,000 µM H2O2 for 1 h significantly reduced CAV‑1 expression levels...
September 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944216/legionella-effector-ankx-disrupts-host-cell-endocytic-recycling-in-a-phosphocholination-dependent-manner
#20
Samual C Allgood, Barbara P Romero Dueñas, Rebecca R Noll, Colleen Pike, Sean Lein, M Ramona Neunuebel
The facultative intracellular bacterium Legionella pneumophila proliferates within amoebae and human alveolar macrophages, and it is the causative agent of Legionnaires' disease, a life-threatening pneumonia. Within host cells, L. pneumophila establishes a replicative haven by delivering numerous effector proteins into the host cytosol, many of which target membrane trafficking by manipulating the function of Rab GTPases. The Legionella effector AnkX is a phosphocholine transferase that covalently modifies host Rab1 and Rab35...
2017: Frontiers in Cellular and Infection Microbiology
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