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Recycling endosomes

Andrea E Toth, Piotr Siupka, Thomas J P Augustine, Susanne T Venø, Louiza B Thomsen, Torben Moos, Hannes T Lohi, Peder Madsen, Karin Lykke-Hartmann, Morten S Nielsen
Receptor- and adsorptive-mediated transport through brain endothelial cells (BEC) of the blood-brain barrier (BBB) involves a complex array of subcellular vesicular structures, the endo-lysosomal system. It consists of several types of vesicles, such as early, recycling, and late endosomes, retromer-positive structures, and lysosomes. Since this system is important for receptor-mediated transcytosis of drugs across brain capillaries, our aim was to characterise the endo-lysosomal system in BEC with emphasis on their interactions with astrocytes...
March 20, 2018: Molecular Neurobiology
Kelly Barford, Austin Keeler, Lloyd McMahon, Kathryn McDaniel, Chan Choo Yap, Christopher D Deppmann, Bettina Winckler
The development of the peripheral nervous system relies on long-distance signaling from target organs back to the soma. In sympathetic neurons, this long-distance signaling is mediated by target derived Nerve Growth Factor (NGF) interacting with its axonal receptor, TrkA. This ligand receptor complex internalizes into what is commonly referred to as the signaling endosome which is transported retrogradely to the soma and dendrites to mediate survival signaling and synapse formation, respectively. The molecular identity of signaling endosomes in dendrites has not yet been determined...
March 16, 2018: Scientific Reports
Alina Fedoseienko, Melinde Wijers, Justina C Wolters, Daphne Dekker, Marieke Smit, Nicolette Huijkman, Niels Kloosterhuis, Helene Klug, Aloys Schepers, Ko Willems van Dijk, Johannes H Levels, Daniel D Billadeau, Marten H Hofker, Jan van Deursen, Marit Westerterp, Ezra Burstein, Jan Albert Kuivenhoven, Bart van de Sluis
<u>Rationale:</u> <u>CO</u> pper<u>M</u>etabolism<u>M</u>URR1 Domain-containing (COMMD) proteins are a part of the COMMD-CCDC22-CCDC93 (CCC) complexes facilitating endosomal trafficking of cell surface receptors. Hepatic COMMD1 inactivation decreases CCDC22 and CCDC93 protein levels, impairs the recycling of the low-density lipoprotein receptor (LDLR), and increases plasma LDL cholesterol levels in mice. However, whether any of the other COMMD members function similarly as COMMD1, and whether perturbation in the CCC complex promotes atherogenesis remain unclear...
March 15, 2018: Circulation Research
A Covarrubias-Pinto, A I Acuña, G Boncompain, E Pápic, P V Burgos, F Perez, M A Castro
Ascorbic acid (Asc) is an antioxidant molecule essential for physiological functions. The concentration of extracellular Asc increases during synaptic transmission and renal reabsorption. These phenomena induce an increase of the Sodium-dependent-Vitamin-C-transporter 2 (SVCT2) at plasma membrane (PM) localization, as we previously demonstrated in neuronal and non-neuronal cells. Hence, the aim of this study was to evaluate intracellular SVCT2 trafficking kinetics in response to Asc. We observed two peaks of SVCT2 localization and function at the PM (at 5-10min, "acute response", and 30-60min, "post-acute response") when cells were incubated with Asc...
March 12, 2018: Free Radical Biology & Medicine
William R Critchley, Caroline Pellet-Many, Benjamin Ringham-Terry, Michael A Harrison, Ian C Zachary, Sreenivasan Ponnambalam
Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes...
March 15, 2018: Cells
Dongfen Yuan, Frederik Rode, Yanguang Cao
We proposed here a minimal physiologically based pharmacokinetic (mPBPK) model for a group of novel engineered antibodies in mice and humans. These antibodies are designed with altered binding properties of their Fc domain with neonatal Fc receptor (FcRn) or the Fab domain with their cognate targets (recycling antibodies) in acidic endosomes. To enable simulations of such binding features in the change of antibody pharmacokinetics and its target suppression, we nested an endothelial endosome compartment in parallel with plasma compartment based on our previously established mPBPK model...
March 14, 2018: AAPS Journal
Mo Chen, Tao Qiu, Jiajie Wu, Yang Yang, Graham D Wright, Min Wu, Ruowen Ge
Classic endocytosis destinations include the recycling endosome returning to the plasma membrane or the late endosome (LE) merging with lysosomes for cargo degradation. However, the anti-angiogenic proteins angiostatin and isthmin, are endocytosed and trafficked to mitochondria (Mito) to execute apoptosis of endothelial cells. How these extracellular proteins reach mitochondria remains a mystery. Through confocal and super-resolution fluorescent microscopy, we demonstrate that angiostatin and isthmin are trafficked to mitochondria through the interaction between LE and Mito...
March 9, 2018: Cell Death and Differentiation
Jenny Chia, Jade Louber, Isabelle Glauser, Shirley Taylor, Greg T Bass, Steve K Dower, Paul A Gleeson, Anne M Verhagen
The neonatal Fc receptor (FcRn) has a pivotal role in albumin and IgG homeostasis. Internalized IgG captured by FcRn under acidic endosomal conditions is recycled to the cell surface where exocytosis and a shift to neutral pH promote extracellular IgG release. Although a similar mechanism is proposed for FcRn-mediated albumin intracellular trafficking and recycling, this pathway is less well defined, but is relevant to the development of therapeutics exploiting FcRn to extend the half-life of short-lived plasma proteins...
March 9, 2018: Journal of Biological Chemistry
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
Gabrielle T Parkinson, Sophie E L Chamberlain, Nadia Jaafari, Matthew Turvey, Jack R Mellor, Jonathan G Hanley
AMPA receptor (AMPAR) trafficking is a key determinant of synaptic strength and synaptic plasticity. Under basal conditions, constitutive trafficking maintains surface AMPARs by internalization into the endosomal system, where the majority are sorted and targeted for recycling back to the plasma membrane. NMDA receptor (NMDAR)-dependent Long-Term Depression (LTD) is characterised by a reduction in synaptic strength, and involves endosomal sorting of AMPARs away from recycling pathways to lysosomes. The mechanisms that determine whether AMPARs are trafficked to lysosomes or to recycling endosomes, especially in response to NMDAR stimulation, are unclear...
March 7, 2018: Scientific Reports
Tomoaki Sobajima, Shin-Ichiro Yoshimura, Tomomi Maeda, Haruhiko Miyata, Eiji Miyoshi, Akihiro Harada
Cholesterol, which is endocytosed to the late endosome (LE)/lysosome, is delivered to other organelles through vesicular and nonvesicular transport mechanisms. In this study, we discuss a novel mechanism of cholesterol transport from recycling endosomes (REs) to the trans-Golgi network (TGN) through RELCH/KIAA1468, which is newly identified in this study as a Rab11-GTP- and OSBP-binding protein. After treating cells with 25-hydroxycholesterol to induce OSBP relocation from the cytoplasm to the TGN, REs accumulated around the TGN area, but this accumulation was diminished in RELCH- or OSBP-depleted cells...
March 7, 2018: Journal of Cell Biology
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
Sho W Suzuki, Scott D Emr
The lysosome (or vacuole in yeast) is the central organelle responsible for cellular degradation and nutrient storage. Lysosomes receive cargo from the secretory, endocytic, and autophagy pathways. Many of these proteins and lipids are delivered to the lysosome membrane, and some are degraded in the lysosome lumen, whereas others appear to be recycled through unknown pathways. In this study, we identify the transmembrane autophagy protein Atg27 as a physiological cargo recycled from the vacuole. We reveal that Atg27 is delivered to the vacuole membrane and then recycled using a two-step recycling process...
March 6, 2018: Journal of Cell Biology
By Sara Woodman, Christopher Trousdale, Justin Conover, Kyoungtae Kim
Protein recycling is an essential cellular process involving endocytosis, intracellular trafficking, and exocytosis. In mammalian systems membrane lipids, including cholesterol, sphingolipids, and phospholipids, play a pivotal role in protein recycling. To address this role in budding yeast, Saccharomyces cerevisiae, we utilized GFP-Snc1, a v-SNARE protein serving as a fluorescent marker for faithfully reporting the recycling pathway. Here we demonstrate results that display moderate to significant GFP-Snc1 recycling defects upon overexpression or inactivation of phospholipid, ergosterol, and sphingolipid biosynthesis enzymes, indicating that the homeostasis of membrane lipid levels is prerequisite for proper protein recycling...
March 3, 2018: Cell Biology International
Jayakumar Vadakekolathu, Shaymaa Ismael Kadhim Al-Juboori, Catherine Johnson, Anne Schneider, Magdalena Elżbieta Buczek, Anna Di Biase, Alan Graham Pockley, Graham Roy Ball, Desmond George Powe, Tarik Regad
Cell-cell adhesions constitute the structural "glue" that retains cells together and contributes to tissue organisation and physiological function. The integrity of these structures is regulated by extracellular and intracellular signals and pathways that act on the functional units of cell adhesion such as the cell adhesion molecules/adhesion receptors, the extracellular matrix (ECM) proteins and the cytoplasmic plaque/peripheral membrane proteins. In advanced cancer, these regulatory pathways are dysregulated and lead to cell-cell adhesion disassembly, increased invasion and metastasis...
March 1, 2018: Cell Death & Disease
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
Ira Milosevic
Without robust mechanisms to efficiently form new synaptic vesicles (SVs), the tens to hundreds of SVs typically present at the neuronal synapse would be rapidly used up, even at modest levels of neuronal activity. SV recycling is thus critical for synaptic physiology and proper function of sensory and nervous systems. Yet, more than four decades after it was originally proposed that the SVs are formed and recycled locally at the presynaptic terminals, the mechanisms of endocytic processes at the synapse are heavily debated...
2018: Frontiers in Cellular Neuroscience
Pierpaolo Ginefra, Bruno G H Filippi, Prudence Donovan, Sylvain Bessonnard, Daniel B Constam
Furin trafficking, and that of related proprotein convertases (PCs), may regulate which substrates are accessible for endoproteolysis, but tools to directly test this hypothesis have been lacking. Here, we develop targeted biosensors that indicate Furin activity in endosomes is 10-fold less inhibited by decanoyl-RVKR-chloromethylketone and enriched >3-fold in endosomes compared to the trans-Golgi network (TGN). Endogenous PC7, which resists this inhibitor, was active in distinct vesicles. Only overexpressed PC7 activity reached the cell surface, endosomes, and the TGN...
February 20, 2018: Cell Reports
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...
February 18, 2018: Biochimica et Biophysica Acta
Michael A Harrison, Steven P Muench
The vacuolar H+ -ATPase (V-ATPase) is a ~1 MDa membrane protein complex that couples the hydrolysis of cytosolic ATP to the transmembrane movement of protons. In essentially all eukaryotic cells, this acid pumping function plays critical roles in the acidification of endosomal/lysosomal compartments and hence in transport, recycling and degradative pathways. It is also important in acid extrusion across the plasma membrane of some cells, contributing to homeostatic control of cytoplasmic pH and maintenance of appropriate extracellular acidity...
2018: Sub-cellular Biochemistry
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