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Endocytic trafficking

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https://www.readbyqxmd.com/read/28334751/atp13a2-park9-regulates-endo-lysosomal-cargo-sorting-and-proteostasis-through-a-novel-pi-3-5-p2-mediated-scaffolding-function
#1
S Demirsoy, S Martin, S Motamedi, S van Veen, T Holemans, C Van den Haute, A Jordanova, V Baekelandt, P Vangheluwe, P Agostinis
ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28301372/news-on-the-molecular-regulation-and-function-of-hepatic-low-density-lipoprotein-receptor-and-ldlr-related-protein-1
#2
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/28298493/deubiquitinating-enzymes-ubp2-and-ubp15-regulate-endocytosis-by-limiting-ubiquitination-and-degradation-of-arts
#3
Hsuan-Chung Ho, Jason A MacGurn, Scott D Emr
Endocytic downregulation of cell-surface proteins is a fundamental cellular process for cell survival and adaptation to environmental stimuli. Ubiquitination of cargo proteins serves as the sorting signal for downstream trafficking, and relies on the Rsp5-ART (arrestin-related trafficking adaptors) ubiquitin ligase adaptor network in yeast. Hence, proper regulation of the abundance and activity of these ligase-adaptor complexes is critical for maintenance of optimal plasma membrane (PM) protein composition...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#4
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28293541/high-content-imaging-reveals-expansion-of-the-endosomal-compartment-during-coxiella-burnetii-parasitophorous-vacuole-maturation
#5
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/28292916/rab-gtpases-master-regulators-that-establish-the-secretory-and-endocytic-pathways
#6
Suzanne R Pfeffer
Several of the most important discoveries in the field of membrane traffic have come from studies of Rab GTPases by Marino Zerial and Peter Novick and their colleagues. Zerial was the first to discover that Rab GTPases represent identity markers for different membrane-bound compartments, and each Rab organizes a collection of specific effectors into function-specifying membrane microdomains to carry out receptor trafficking. Novick discovered that the order (and thus polarity) of Rab GTPases along the secretory and endocytic pathways are established by their specific, cognate guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which partner with one Rab to regulate the subsequent- and prior-acting Rabs...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28286744/endocytic-trafficking-at-the-mature-podocyte-slit-diaphragm
#7
REVIEW
Agnieszka Swiatecka-Urban
Endocytic trafficking couples cell signaling with the cytoskeletal dynamics by organizing a crosstalk between protein networks in different subcellular compartments. Proteins residing in the plasma membrane are internalized and transported as cargo in endocytic vesicles (i.e., endocytosis). Subsequently, cargo proteins can be delivered to lysosomes for degradation or recycled back to the plasma membrane. The slit diaphragm is a modified tight junction connecting foot processes of the glomerular epithelial cells, podocytes...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28285997/ccm-3-promotes-c-%C3%A2-elegans-germline-development-by-regulating-vesicle-trafficking-cytokinesis-and-polarity
#8
Swati Pal, Benjamin Lant, Bin Yu, Ruilin Tian, Jiefei Tong, Jonathan R Krieger, Michael F Moran, Anne-Claude Gingras, W Brent Derry
Cerebral cavernous malformations (CCMs) are vascular defects of the CNS that arise from loss of integrity of the endothelial cells lining blood capillaries, causing leakage of blood into the brain [1]. This results in headaches, seizures, and/or hemorrhagic stroke, depending on the location of the lesion. CCM affects 0.5% of the population and follows an autosomal dominant inheritance pattern caused by mutations in one of the three genes: CCM1 (gene name KRIT1), CCM2 (also known as malcavernin or OSM), and CCM3 (gene name PDCD10) [2, 3], with the earliest onset and most severe prognosis occurring in CCM3 patients [4]...
March 20, 2017: Current Biology: CB
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
#9
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/28273137/adaptor-protein-3-a-key-player-in-rbl-2h3-mast-cell-mediator-release
#10
Elaine Zayas Marcelino da Silva, Edismauro Garcia Freitas-Filho, Devandir Antonio de Souza-Júnior, Luis Lamberti Pinto daSilva, Maria Celia Jamur, Constance Oliver
Mast cell (MC) secretory granules are Lysosome-Related Organelles (LROs) whose biogenesis is associated with the post-Golgi secretory and endocytic pathways in which the sorting of proteins destined for a specific organelle relies on the recognition of sorting signals by adaptor proteins that direct their incorporation into transport vesicles. The adaptor protein 3 (AP-3) complex mediates protein trafficking between the trans-Golgi network (TGN) and late endosomes, lysosomes, and LROs. AP-3 has a recognized role in LROs biogenesis and regulated secretion in several cell types, including many immune cells such as neutrophils, natural killer cells, and cytotoxic T lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28264927/missing-in-metastasis-protein-downregulates-cxcr4-by-promoting-ubiquitination-and-interaction-with-small-rab-gtpases
#11
Lushen Li, Shaneen S Baxter, Ning Gu, Min Ji, Xi Zhan
Surface expression of chemokine receptor CXCR4 is downregulated by MIM, a member of the inverse BAR (I-BAR) domain protein family that recognizes and generates membranes with negative curvatures. Yet, the mechanism for the regulation is unknown. Here, we showed that MIM formed a complex with CXCR4 via binding to E3 ubiquitin ligase AIP4 in response to SDF-1. Overexpression of MIM promoted CXCR4 ubiquitination, inhibited cellular response to SDF-1, caused accumulation and aggregation of MVBs in the cytoplasm, and promoted CXCR4 sorting into MVBs in a manner depending on binding to AIP4...
March 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28250131/measles-virus-enters-breast-and-colon-cancer-cell-lines-through-a-pvrl4-mediated-macropinocytosis-pathway
#12
Sebastien Delpeut, Gary Sisson, Karen M Black, Christopher D Richardson
Measles virus (MeV) is a member of the family Paramixoviridae that causes a highly contagious respiratory disease, but has emerged as a promising oncolytic platform. Previous studies of MeV entry have focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express MeV receptors, SLAM (Signaling Lymphocyte-Activating Molecule) and PVRL4 (Poliovirus Receptor-Like-4, nectin-4)...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28226233/chemical-genetic-dissection-of-membrane-trafficking
#13
Lorena Norambuena, Ricardo Tejos
The plant endomembrane system is an extensively connected functional unit for exchanging material between compartments. Secretory and endocytic pathways allow dynamic trafficking of proteins, lipids, and other molecules, regulating a myriad of biological processes. Chemical genetics-the use of compounds to perturb biological processes in a fast, tunable, and transient manner-provides elegant tools for investigating this system. Here, we review how chemical genetics has helped to elucidate different aspects of membrane trafficking...
February 13, 2017: Annual Review of Plant Biology
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#14
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28224002/secretion-and-endocytosis-in-pollen-tubes-models-of-tip-growth-in-the-spot-light
#15
REVIEW
Gleb Grebnev, Maria Ntefidou, Benedikt Kost
Pollen tube tip growth is a widely used model ideally suited to study cellular processes underlying polarized cell expansion. Local secretion supplying material for plasma membrane (PM) and cell wall extension is essential for this process. Cell wall biogenesis requires fusion of secretory vesicles with the PM at an about 10× higher rate than PM extension. Excess material is therefore incorporated into the PM, which needs to be reinternalized through endocytosis. The classical model of tip growth proposes that exocytosis occurs at the apex and that newly incorporated PM material is transported to adjacent lateral regions, where excess material is endocytically recycled...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223337/functional-expression-of-dopamine-d2-receptor-is-regulated-by-tetraspanin-7-mediated-postendocytic-trafficking
#16
Seol-Ae Lee, Yeongjun Suh, Saebom Lee, Jaehoon Jeong, Soo Jeong Kim, So Jung Kim, Sang Ki Park
The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28220414/quantitative-analysis-of-ligand-induced-endocytosis-of-flagellin-sensing-2-using-automated-image-segmentation
#17
Michelle E Leslie, Antje Heese
Plants are equipped with a suite of plant pattern recognition receptors (PRRs) that must be properly trafficked to and from the plasma membrane (PM), which serves as the host-pathogen interface, for robust detection of invading pathogenic microbes. Recognition of bacterial flagellin, or the derived peptide flg22, is facilitated by the PM-localized PRR, FLAGELLIN SENSING 2 (FLS2). Upon flg22 binding, FLS2 is rapidly internalized from the PM into endosomal compartments and subsequently degraded. To understand better the integration of FLS2 endocytosis and signaling outputs, we developed methods for the quantitative analysis of FLS2 trafficking using freely available bioimage informatic tools...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28199211/endocytosis-and-membrane-receptor-internalization-implication-of-f-bar-protein-carom
#18
Yanjie Xu, Jixiang Xia, Suxuan Liu, Sam Stein, Cueto Ramon, Hang Xi, Luqiao Wang, Xinyu Xiong, Lixiao Zhang, Dingwen He, William Yang, Xianxian Zhao, Xiaoshu Cheng, Xiaofeng Yang, Hong Wang
Endocytosis is a cellular process mostly responsible for membrane receptor internalization. Cell membrane receptors bind to their ligands and form a complex which can be internalized. We previously proposed that F-BAR protein initiates membrane curvature and mediates endocytosis via its binding partners. However, F-BAR protein partners involved in membrane receptor endocytosis and the regulatory mechanism remain unknown. In this study, we established database mining strategies to explore mechanisms underlying receptor-related endocytosis...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28171750/crosstalk-between-clcb-dyn1-mediated-adaptive-clathrin-mediated-endocytosis-and-epidermal-growth-factor-receptor-signaling-increases-metastasis
#19
Ping-Hung Chen, Nawal Bendris, Yi-Jing Hsiao, Carlos R Reis, Marcel Mettlen, Hsuan-Yu Chen, Sung-Liang Yu, Sandra L Schmid
Signaling receptors are internalized and regulated by clathrin-mediated endocytosis (CME). Two clathrin light chain isoforms, CLCa and CLCb, are integral components of the endocytic machinery whose differential functions remain unknown. We report that CLCb is specifically upregulated in non-small-cell lung cancer (NSCLC) cells and is associated with poor patient prognosis. Engineered single CLCb-expressing NSCLC cells, as well as "switched" cells that predominantly express CLCb, exhibit increased rates of CME and altered clathrin-coated pit dynamics...
February 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28159908/regulation-of-synaptic-amyloid-%C3%AE-generation-through-bace1-retrograde-transport-in-a-mouse-model-of-alzheimer-s-disease
#20
Xuan Ye, Tuancheng Feng, Prasad Tammineni, Qing Chang, Yu Young Jeong, David J Margolis, Huaibin Cai, Alexander Kusnecov, Qian Cai
Amyloid-β (Aβ) peptides play a key role in synaptic damage and memory deficits in the early pathogenesis of Alzheimer's disease (AD). Abnormal accumulation of Aβ at nerve terminals leads to synaptic pathology and ultimately to neurodegeneration. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal β-secretase for Aβ generation. However, the mechanisms regulating BACE1 distribution in axons and β cleavage of APP at synapses remain largely unknown. Here, we reveal that dynein-Snapin-mediated retrograde transport regulates BACE1 trafficking in axons and APP processing at presynaptic terminals...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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