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Transferrin Recycling

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https://www.readbyqxmd.com/read/30025247/receptor-mediated-transcytosis-in-biological-barrier-the-influence-of-receptor-character-and-their-ligand-density-on-the-transmembrane-pathway-of-active-targeting-nanocarriers
#1
Xiaoning Song, Rui Li, Hailiang Deng, Ye Li, Yanan Cui, Hua Zhang, Wenbing Dai, Bing He, Ying Zheng, Xueqing Wang, Qiang Zhang
Active-targeting nanocarriers can significantly improve the transcytosis of poorly water-soluble or bio-macromolecular drugs across biological barrier. However, reasons for the improvement are not understood enough, which hampered the reasonable design of active targeting nanocarriers. To illustrate how different factors influence the transport of active-targeting nanocarriers, we established ligand-decorated micelles targeting different receptors to study how the decorations influence the transcytosis of the micelles by comparing the endocytosis, transport pathway and exocytosis process...
October 2018: Biomaterials
https://www.readbyqxmd.com/read/29997525/epithelial-na-channel-reciprocal-control-by-commd10-and-nedd4-2
#2
Adam W Ware, Tanya T Cheung, Sahib Rasulov, Ezra Burstein, Fiona J McDonald
Optimal function of the epithelial sodium channel (ENaC) in the distal nephron is key to the kidney's long-term control of salt homeostasis and blood pressure. Multiple pathways alter ENaC cell surface populations, including correct processing and trafficking in the secretory pathway to the cell surface, and retrieval from the cell surface through ubiquitination by the ubiquitin ligase Nedd4-2, clathrin-mediated endocytosis, and sorting in the endosomal system. Members of the Copper Metabolism Murr1 Domain containing (COMMD) family of 10 proteins are known to interact with ENaC...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29970615/an-oxanthroquinone-derivative-that-disrupts-ras-plasma-membrane-localization-inhibits-cancer-cell-growth
#3
Lingxiao Tan, Kwang-Jin Cho, Pratik Neupane, Robert J Capon, John F Hancock
Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examine the mechanism of action of oxanthroquinone G01 (G01), a recently described inhibitor of KRAS PM localization. We show that G01 mislocalizes HRAS and KRAS from the PM with similar potency and disrupts the spatial organization of RAS proteins remaining on the PM...
July 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29958948/wip-itsn1-complex-is-involved-in-cellular-vesicle-trafficking-and-formation-of-filopodia-like-protrusions
#4
Tetyana Gryaznova, Olga Gubar, Mariia Burdyniuk, Sergii Kropyvko, Alla Rynditch
WIP (WASP interacting protein) together with N-WASP (neural Wiskott-Aldrich syndrome protein) regulates actin polymerization that is crucial for invadopodia and filopodia formation. Recently, we reported the WIP interaction with ITSN1 which is highly implicated in endo-/exocytosis, apoptosis, mitogenic signaling and cytoskeleton rearrangements. Here we demonstrate that the WIP/ITSN1 complex is involved in the transferrin receptor recycling and partially co-localizes with a marker of the fast recycling endosomes, RAB4...
June 26, 2018: Gene
https://www.readbyqxmd.com/read/29953492/simple-binds-specifically-to-pi4p-through-simple-like-domain-and-participates-in-protein-trafficking-in-the-trans-golgi-network-and-or-recycling-endosomes
#5
Yasuhiro Moriwaki, Yuho Ohno, Tomohiro Ishii, Yuki Takamura, Yuko Kita, Kazuhiko Watabe, Kazunori Sango, Shoutaro Tsuji, Hidemi Misawa
Small integral membrane protein of the lysosome/late endosome (SIMPLE) is a 161-amino acid cellular protein that contains a characteristic C-terminal domain known as the SIMPLE-like domain (SLD), which is well conserved among species. Several studies have demonstrated that SIMPLE localizes to the trans-Golgi network (TGN), early endosomes, lysosomes, multivesicular bodies, aggresomes and the plasma membrane. However, the amino acid regions responsible for its subcellular localization have not yet been identified...
2018: PloS One
https://www.readbyqxmd.com/read/29891722/hrs-wash-axis-governs-actin-mediated-endosomal-recycling-and-cell-invasion
#6
Ewan MacDonald, Louise Brown, Arnaud Selvais, Han Liu, Thomas Waring, Daniel Newman, Jessica Bithell, Douglas Grimes, Sylvie Urbé, Michael J Clague, Tobias Zech
Transmembrane proteins in the sorting endosome are either recycled to their point of origin or destined for lysosomal degradation. Lysosomal sorting is mediated by interaction of ubiquitylated transmembrane proteins with the endosomal sorting complex required for transport (ESCRT) machinery. In this study, we uncover an alternative role for the ESCRT-0 component hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) in promoting the constitutive recycling of transmembrane proteins. We find that endosomal localization of the actin nucleating factor Wiscott-Aldrich syndrome protein and SCAR homologue (WASH) requires HRS, which occupies adjacent endosomal subdomains...
July 2, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29759989/novel-regulation-of-integrin-trafficking-by-rab11-fip5-in-aggressive-prostate-cancer
#7
Lipsa Das, Jaime M C Gard, Rytis Prekeris, Raymond B Nagle, Colm Morrissey, Beatrice S Knudsen, Cindy K Miranti, Anne E Cress
The laminin-binding integrins, α3β1 and α6β1, are needed for tumor metastasis and their surface expression is regulated by endocytic recycling. β1 integrins share the Rab11 recycling machinery, but the trafficking of α3β1 and α6β1 are distinct by an unknown mechanism. Using a mouse PDX tumor model containing human metastatic prostate cancer, Rab11 family interacting protein 5 (Rab11-FIP5) was identified as a lead candidate for α6β1 trafficking. Rab11-FIP5 and its membrane-binding domain were required for α6β1 recycling, without affecting the other laminin-binding integrin (i...
May 14, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29668757/actin-polymerization-in-the-endosomal-pathway-but-not-on-the-coxiella-containing-vacuole-is-essential-for-pathogen-growth
#8
Heather E Miller, Charles L Larson, Robert A Heinzen
Coxiella burnetii is an intracellular bacterium that replicates within an expansive phagolysosome-like vacuole. Fusion between the Coxiella-containing vacuole (CCV) and late endosomes/multivesicular bodies requires Rab7, the HOPS tethering complex, and SNARE proteins, with actin also speculated to play a role. Here, we investigated the importance of actin in CCV fusion. Filamentous actin patches formed around the CCV membrane that were preferred sites of vesicular fusion. Accordingly, the mediators of endolysosomal fusion Rab7, VAMP7, and syntaxin 8 were concentrated in CCV actin patches...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29659573/whole-body-iron-transport-and-metabolism-mechanistic-multi-scale-model-to-improve-treatment-of-anemia-in-chronic-kidney-disease
#9
Joydeep Sarkar, Alka A Potdar, Gerald M Saidel
Iron plays vital roles in the human body including enzymatic processes, oxygen-transport via hemoglobin and immune response. Iron metabolism is characterized by ~95% recycling and minor replenishment through diet. Anemia of chronic kidney disease (CKD) is characterized by a lack of synthesis of erythropoietin leading to reduced red blood cell (RBC) formation and aberrant iron recycling. Treatment of CKD anemia aims to normalize RBC count and serum hemoglobin. Clinically, the various fluxes of iron transport and accumulation are not measured so that changes during disease (e...
April 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29590595/entropic-control-of-receptor-recycling-using-engineered-ligands
#10
Andre C M DeGroot, David J Busch, Carl C Hayden, Samuel A Mihelic, Aaron T Alpar, Marcelo Behar, Jeanne C Stachowiak
Receptor internalization by endocytosis regulates diverse cellular processes, from the rate of nutrient uptake to the timescale of essential signaling events. The established view is that internalization is tightly controlled by specific protein-binding interactions. However, recent work suggests that physical aspects of receptors influence the process in ways that cannot be explained by biochemistry alone. Specifically, work from several groups suggests that increasing the steric bulk of receptors may inhibit their uptake by multiple types of trafficking vesicles...
March 27, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29582527/rab11-mediates-selective-recycling-and-endocytic-trafficking-in-trypanosoma-brucei
#11
Khan Umaer, Peter J Bush, James D Bangs
Trypanosoma brucei possesses a streamlined secretory system that guarantees efficient delivery to the cell surface of the critical glycosyl-phosphatidylinositol (GPI)-anchored virulence factors, variant surface glycoprotein (VSG) and transferrin receptor (TfR). Both are thought to be constitutively endocytosed and returned to the flagellar pocket via TbRab11+ recycling endosomes. We use conditional knockdown with established reporters to investigate the role of TbRab11 in specific endomembrane trafficking pathways in bloodstream trypanosomes...
June 2018: Traffic
https://www.readbyqxmd.com/read/29515184/alteration-of-endosomal-trafficking-is-associated-with-early-onset-parkinsonism-caused-by-synj1-mutations
#12
Dominga Fasano, Silvia Parisi, Giovanna Maria Pierantoni, Anna De Rosa, Marina Picillo, Giuseppina Amodio, Maria Teresa Pellecchia, Paolo Barone, Ornella Moltedo, Vincenzo Bonifati, Giuseppe De Michele, Lucio Nitsch, Paolo Remondelli, Chiara Criscuolo, Simona Paladino
Recently, a new form of autosomal recessive early-onset parkinsonism (PARK20), due to mutations in the gene encoding the phosphoinositide phosphatase, Synaptojanin 1 (Synj1), has been reported. Several genes responsible for hereditary forms of Parkinson's disease are implicated in distinct steps of the endolysosomal pathway. However, the nature and the degree of endocytic membrane trafficking impairment in early-onset parkinsonism remains elusive. Here, we show that depletion of Synj1 causes drastic alterations of early endosomes, which become enlarged and more numerous, while it does not affect the morphology of late endosomes both in non-neuronal and neuronal cells...
March 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29476049/vps3-and-vps8-control-integrin-trafficking-from-early-to-recycling-endosomes-and-regulate-integrin-dependent-functions
#13
C T H Jonker, R Galmes, T Veenendaal, C Ten Brink, R E N van der Welle, N Liv, J de Rooij, A A Peden, P van der Sluijs, C Margadant, J Klumperman
Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes...
February 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29466707/iron-transport-kinetics-through-blood-brain-barrier-endothelial-cells
#14
Aminul Islam Khan, Jin Liu, Prashanta Dutta
BACKGROUND: Transferrin and its receptors play an important role during the uptake and transcytosis of iron through blood-brain barrier (BBB) endothelial cells (ECs) to maintain iron homeostasis in BBB endothelium and brain. Any disruptions in the cell environment may change the distribution of transferrin receptors on the cell surface, which eventually alter the homeostasis and initiate neurodegenerative disorders. In this paper, we developed a comprehensive mathematical model that considers the necessary kinetics for holo-transferrin internalization and acidification, apo-transferrin recycling, and exocytosis of free iron and transferrin-bound iron through basolateral side of BBB ECs...
May 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29466231/transcytosis-of-payloads-that-are-non-covalently-complexed-to-bispecific-antibodies-across-the-hcmec-d3-blood-brain-barrier-model
#15
Daniela Schmid, Annette Buntz, Thi Ngoc Hanh Phan, Klaus Mayer, Eike Hoffmann, Irmgard Thorey, Jens Niewöhner, Katrin Vasters, Ranjan Sircar, Olaf Mundigl, Roland E Kontermann, Ulrich Brinkmann
A transcellular shuttle system was generated for the delivery of non-covalently linked payloads across blood-brain barrier (BBB) endothelial cells. Transcytosis-enabling shuttles are composed of bispecific antibodies (bsAbs) that simultaneously bind transferrin receptor (TfR) and haptens such as digoxigenin or biocytinamide. Haptenylated payloads are attached to these vehicles via non-covalent hapten-antibody complexation. This enables targeting to and internalization into human BBB-derived microvascular endothelial hCMEC/D3 cells...
June 27, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29395073/impaired-transferrin-receptor-palmitoylation-and-recycling-in-neurodegeneration-with-brain-iron-accumulation
#16
Anthony Drecourt, Joël Babdor, Michael Dussiot, Floriane Petit, Nicolas Goudin, Meriem Garfa-Traoré, Florence Habarou, Christine Bole-Feysot, Patrick Nitschké, Chris Ottolenghi, Metodi D Metodiev, Valérie Serre, Isabelle Desguerre, Nathalie Boddaert, Olivier Hermine, Arnold Munnich, Agnès Rötig
Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous condition characterized by progressive dystonia with iron accumulation in the basal ganglia. How NBIA-associated mutations trigger iron overload remains poorly understood. After studying fibroblast cell lines from subjects carrying both known and unreported biallelic mutations in CRAT and REPS1, we ascribe iron overload to the abnormal recycling of transferrin receptor (TfR1) and the reduction of TfR1 palmitoylation in NBIA...
February 1, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29296759/a-specialized-pathway-for-erythroid-iron-delivery-through-lysosomal-trafficking-of-transferrin-receptor-2
#17
Shadi Khalil, Maja Holy, Stephen Grado, Robert Fleming, Ryo Kurita, Yukio Nakamura, Adam Goldfarb
Erythroid progenitors are the largest consumers of iron in the human body. In these cells, a high flux of iron must reach the mitochondrial matrix to form sufficient heme to support hemoglobinization. Canonical erythroid iron trafficking occurs via the first transferrin receptor (TfR1)-mediated endocytosis of diferric-transferrin into recycling endosomes, where ferric iron is released, reduced, and exported to the cytosol via DMT1. However, mice lacking TfR1 or DMT1 demonstrate residual erythropoiesis, suggesting additional pathways for iron use...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29203237/adiponectin-release-and-insulin-receptor-targeting-share-trans-golgi-dependent-endosomal-trafficking-routes
#18
Maria Rödiger, Martin W Werno, Ilka Wilhelmi, Christian Baumeier, Deike Hesse, Nina Wettschureck, Stefan Offermanns, Kyungyeun Song, Michael Krauß, Annette Schürmann
OBJECTIVE: Intracellular vesicle trafficking maintains cellular structures and functions. The assembly of cargo-laden vesicles at the trans-Golgi network is initiated by the ARF family of small GTPases. Here, we demonstrate the role of the trans-Golgi localized monomeric GTPase ARFRP1 in endosomal-mediated vesicle trafficking of mature adipocytes. METHODS: Control (Arfrp1flox/flox ) and inducible fat-specific Arfrp1 knockout (Arfrp1iAT-/- ) mice were metabolically characterized...
February 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29054881/ablation-of-tfr1-in-purkinje-cells-inhibits-mglu1-trafficking-and-impairs-motor-coordination-but-not-autistic-like-behaviors
#19
Jia-Huan Zhou, Xin-Tai Wang, Liang Zhou, Lin Zhou, Fang-Xiao Xu, Li-Da Su, Hao Wang, Fan Jia, Fu-Qiang Xu, Gui-Quan Chen, Chris I De Zeeuw, Ying Shen
Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28982325/serum-free-or-not-two-distinct-recycling-mechanisms-mediated-by-alpha-v-beta-3-integrin
#20
Yanan Cui, Suxin Li, Binlong Chen, Bing He, Lan Yuan, Wenbing Dai, Hua Zhang, Xueqing Wang, Qiang Zhang
BACKGROUND: Among the many researches on cellular uptake and intracellular trafficking pathways of αvβ3-targeted nanomedicines, a large number of studies utilize serum-free medium to evaluate drug effects and cellular mechanisms in vitro whether the medium is serum free or not has not been paid much attention. METHODS: The aim of this study was to assess the impact of serum on αvβ3-mediated endocytosis and intracellular trafficking pathways. cRGDfK conjugated with Alexa Fluor® 555 was used to recognize αvβ3 integrins specifically...
November 10, 2017: Current Pharmaceutical Biotechnology
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