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Recycling endosome

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https://www.readbyqxmd.com/read/29239314/taking-out-the-garbage-cathepsin-d-and-calcineurin-in-neurodegeneration
#1
REVIEW
Andreas Aufschnaiter, Verena Kohler, Sabrina Büttner
Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson's, Alzheimer's and Huntington's diseases...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29237845/human-cytomegalovirus-replication-is-inhibited-by-the-autophagy-inducing-compounds-trehalose-and-smer28-through-distinctively-different-mechanisms
#2
Alex E Clark, Maite Sabalza, Philip L S M Gordts, Deborah H Spector
Human Cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously published that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles, and that debris, including debris consistent in appearance with abnormal virions, is present in multivesicular bodies...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237816/glycogen-synthase-kinase-3%C3%AE-inhibition-enhances-notch1-recycling
#3
Li Zheng, Sean D Conner
The Notch signaling pathway is essential throughout development and continues into adulthood where it performs a critical role in tissue homeostasis. The fact that defects in signaling can lead to malignancy illustrate the need to tightly control Notch activity. GSK3β is an established regulator of the Notch signaling pathway, although its mechanism of action remains unclear. Given the emerging role for GSK3β in receptor trafficking, we tested the idea that GSK3β controls signaling by regulating Notch transport...
December 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29234936/a-generic-whole-body-physiologically-based-pharmacokinetic-model-for-therapeutic-proteins-in-pk-sim
#4
Christoph Niederalt, Lars Kuepfer, Juri Solodenko, Thomas Eissing, Hans-Ulrich Siegmund, Michael Block, Stefan Willmann, Jörg Lippert
Proteins are an increasingly important class of drugs used as therapeutic as well as diagnostic agents. A generic physiologically based pharmacokinetic (PBPK) model was developed in order to represent at whole body level the fundamental mechanisms driving the distribution and clearance of large molecules like therapeutic proteins. The model was built as an extension of the PK-Sim model for small molecules incorporating (i) the two-pore formalism for drug extravasation from blood plasma to interstitial space, (ii) lymph flow, (iii) endosomal clearance and (iv) protection from endosomal clearance by neonatal Fc receptor (FcRn) mediated recycling as especially relevant for antibodies...
December 12, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29233918/rhob-controls-the-rab11-mediated-recycling-and-surface-reappearance-of-lfa-1-in-migrating-t-lymphocytes
#5
Malin Samuelsson, Katarzyna Potrzebowska, Janne Lehtonen, Jason P Beech, Ekatarina Skorova, Heli Uronen-Hansson, Lena Svensson
The regulation of cell adhesion and motility is complex and requires the intracellular trafficking of integrins to and from sites of cell adhesion, especially in fast-moving cells such as leukocytes. The Rab family of guanosine triphosphatases (GTPases) is essential for vesicle transport, and vesicles mediate intracellular integrin trafficking. We showed that RhoB regulates the vesicular transport of the integrin LFA-1 along the microtubule network in migrating T lymphocytes. Impairment in RhoB function resulted in the accumulation of both LFA-1 and the recycling endosomal marker Rab11 at the rear of migrating T lymphocytes and decreased the association between these molecules...
December 12, 2017: Science Signaling
https://www.readbyqxmd.com/read/29229824/molecular-mechanism-for-the-subversion-of-the-retromer-coat-by-the-legionella-effector-ridl
#6
Miguel Romano-Moreno, Adriana L Rojas, Chad D Williamson, David C Gershlick, María Lucas, Michail N Isupov, Juan S Bonifacino, Matthias P Machner, Aitor Hierro
Microbial pathogens employ sophisticated virulence strategies to cause infections in humans. The intracellular pathogen Legionella pneumophila encodes RidL to hijack the host scaffold protein VPS29, a component of retromer and retriever complexes critical for endosomal cargo recycling. Here, we determined the crystal structure of L. pneumophila RidL in complex with the human VPS29-VPS35 retromer subcomplex. A hairpin loop protruding from RidL inserts into a conserved pocket on VPS29 that is also used by cellular ligands, such as Tre-2/Bub2/Cdc16 domain family member 5 (TBC1D5) and VPS9-ankyrin repeat protein for VPS29 binding...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29226112/formation-of-the-legionella-replicative-compartment-at-the-crossroads-of-retrograde-trafficking
#7
REVIEW
Kevin Bärlocher, Amanda Welin, Hubert Hilbi
Retrograde trafficking from the endosomal system through the Golgi apparatus back to the endoplasmic reticulum is an essential pathway in eukaryotic cells, serving to maintain organelle identity and to recycle empty cargo receptors delivered by the secretory pathway. Intracellular replication of several bacterial pathogens, including Legionella pneumophila, is restricted by the retrograde trafficking pathway. L. pneumophila employs the Icm/Dot type IV secretion system (T4SS) to form the replication-permissive Legionella-containing vacuole (LCV), which is decorated with multiple components of the retrograde trafficking machinery as well as retrograde cargo receptors...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29225077/structural-insights-into-the-ph-dependent-conformational-change-and-collagen-recognition-of-the-human-mannose-receptor
#8
Zhenzheng Hu, Xiangyi Shi, Bowen Yu, Na Li, Ying Huang, Yongning He
Mannose receptor (MR, CD206) is an endocytic receptor on microphages and dendritic cells. It recognizes multiple ligands and plays important roles in regulating immune responses and maintaining glycoprotein homeostasis. However, the structure and functional mechanism of MR remain unclear. Here we determine the crystal structures of the N-terminal fragments of MR and reveal the potential binding mode of collagen on the fibronectin II domain. The SAXS and other biophysical data suggest that MR adopts an extended conformation at physiological pH and undergoes conformational changes as pH decreases, resulting in a compact conformation in an acidic environment...
December 6, 2017: Structure
https://www.readbyqxmd.com/read/29212940/hiv-1-envelope-glycoprotein-trafficking-through-the-endosomal-recycling-compartment-is-required-for-particle-incorporation
#9
Junghwa Kirschman, Mingli Qi, Lingmei Ding, Jason Hammonds, Krista Dienger-Stambaugh, Jaang-Jiun Wang, Lynne A Lapierre, James R Goldenring, Paul Spearman
The HIV-1 envelope glycoprotein (Env) encodes specific trafficking signals within its long cytoplasmic tail (CT) that regulate incorporation into HIV-1 particles. Rab11-Family Interacting Protein 1C (FIP1C) and Rab14 are host trafficking factors required for Env particle incorporation, suggesting that Env undergoes sorting from the endosomal recycling compartment (ERC) to the site of particle assembly on the plasma membrane. We disrupted outward sorting from the ERC by expressing a C-terminal fragment of FIP1C (FIP1C560-649) and examined the consequences on Env trafficking and incorporation into particles...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212031/integration-of-gpcr-signaling-and-sorting-from-very-early-endosomes-via-opposing-appl1-mechanisms
#10
Silvia Sposini, Frederic G Jean-Alphonse, Mohammed A Ayoub, Affiong Oqua, Camilla West, Stuart Lavery, Jan J Brosens, Eric Reiter, Aylin C Hanyaloglu
Endocytic trafficking is a critical mechanism for cells to decode complex signaling pathways, including those activated by G-protein-coupled receptors (GPCRs). Heterogeneity in the endosomal network enables GPCR activity to be spatially restricted between early endosomes (EEs) and the recently discovered endosomal compartment, the very early endosome (VEE). However, the molecular machinery driving GPCR activity from the VEE is unknown. Using luteinizing hormone receptor (LHR) as a prototype GPCR for this compartment, along with additional VEE-localized GPCRs, we identify a role for the adaptor protein APPL1 in rapid recycling and endosomal cAMP signaling without impacting the EE-localized β2-adrenergic receptor...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29210641/dynamic-localization-of-hepatocellular-transporters-role-in-biliary-excretion-and-impairment-in-cholestasis
#11
Marcelo Gabriel Roma, Ismael R Barosso, Gisel S Miszczuk, Fernando A Crocenzi, Enrique J Sanchez Pozzi
Bile flow generation is driven by the vectorial transfer of osmotically active compounds from sinusoidal blood into a confined space, the bile canaliculus. Hence, localization of hepatocellular transporters relevant to bile formation is crucial for bile secretion. Hepatocellular transporters are localized either in the plasma membrane or in recycling endosomes, from where they can be relocated to the plasma membrane on demand, or endocytosed when the demand decreases. The balance between endocytic internalization/exocytic targeting to/from this recycling compartment is therefore the main determinant of the hepatic capability to generate bile, and to dispose endo- and xenobiotics...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29204877/how-multi-scale-structural-biology-elucidated-context-dependent-variability-in-ectodomain-conformation-along-with%C3%A2-the-ligand-capture-and-release-cycle-for-ldlr-family-members
#12
REVIEW
Terukazu Nogi
The low-density lipoprotein receptor (LDLR) and its homologs capture and internalize lipoproteins into the cell. Due to the fact that LDLR family members possess a modular ectodomain that undergoes dynamic conformational changes, multi-scale structural analysis has been performed so as to understand the ligand capture and release mechanism. For example, crystallographic analyses have provided models for both the entire ectodomain and high-resolution structures of individual modules. In addition, nuclear magnetic resonance spectroscopic analyses have shown the rigidity and flexibility of inter-module linkers to restrict the mobility of ectodomain...
December 4, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/29203237/adiponectin-release-and-insulin-receptor-targeting-share-trans-golgi-dependent-endosomal-trafficking-routes
#13
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...
November 22, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29189775/visualizing-endocytic-recycling-and-trafficking-in-live-neurons-by-subdiffractional-tracking-of-internalized-molecules
#14
Merja Joensuu, Ramon Martínez-Mármol, Pranesh Padmanabhan, Nick R Glass, Nela Durisic, Matthew Pelekanos, Mahdie Mollazade, Giuseppe Balistreri, Rumelo Amor, Justin J Cooper-White, Geoffrey J Goodhill, Frédéric A Meunier
Our understanding of endocytic pathway dynamics is restricted by the diffraction limit of light microscopy. Although super-resolution techniques can overcome this issue, highly crowded cellular environments, such as nerve terminals, can also dramatically limit the tracking of multiple endocytic vesicles such as synaptic vesicles (SVs), which in turn restricts the analytical dissection of their discrete diffusional and transport states. We recently introduced a pulse-chase technique for subdiffractional tracking of internalized molecules (sdTIM) that allows the visualization of fluorescently tagged molecules trapped in individual signaling endosomes and SVs in presynapses or axons with 30- to 50-nm localization precision...
December 2017: Nature Protocols
https://www.readbyqxmd.com/read/29169913/the-strategic-function-of-the-p5-atpase-atp13a2-in-toxic-waste-disposal
#15
Felicitas de Tezanos Pinto, Hugo Pedro Adamo
The P-type ATPase ATP13A2 protein was originally associated with a form of Parkinson's Disease (PD) known as Kufor Rakeb Syndrome (KRS). However, in the last years it has been found to underlay variants of neuronal ceroid-lipofuscinoses and hereditary spastic paraplegia. These findings expand the clinical and genetic spectrum of ATP13A2-associated disorders, which are commonly characterized by lysosomal dysfunction. Nowadays it is well known that lysosomes are not merely related to the degradation and recycling of cellular waste, but are also involved in fundamental processes such as secretion, plasma membrane repair, signaling, energy metabolism and autophagy...
November 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29166605/l-type-voltage-gated-ca-2-channels-regulate-synaptic-activity-triggered-recycling-endosome-fusion-in-neuronal-dendrites
#16
Brian G Hiester, Ashley M Bourke, Brooke L Sinnen, Sarah G Cook, Emily S Gibson, Katharine R Smith, Matthew J Kennedy
The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs) with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca(2+) from distinct sources. NMDA receptor Ca(2+) initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca(2+) channels (L-VGCCs) regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29161566/endosomal-trafficking-retromer-and-retriever-are%C3%A2-relatives-in-recycling
#17
David C Gershlick, María Lucas
Transmembrane proteins are sorted from endosomes to avoid lysosomal degradation. A recent study has identified a new multimeric complex called retriever that is essential for recycling numerous cell-surface cargoes from endosomes and is structurally and functionally related to the well-characterised retromer complex.
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29158324/control-of-rab7-activity-and-localization-through-the-retromer-tbc1d5-complex-enables-rab7-dependent-mitophagy
#18
Ana Jimenez-Orgaz, Arunas Kvainickas, Heike Nägele, Justin Denner, Stefan Eimer, Jörn Dengjel, Florian Steinberg
Retromer is an endosomal multi-protein complex that organizes the endocytic recycling of a vast range of integral membrane proteins. Here, we establish an additional retromer function in controlling the activity and localization of the late endosomal small GTPase RAB7. Surprisingly, we found that RAB7 not only decorates late endosomes or lysosomes, but is also present on the endoplasmic reticulum, trans-Golgi network, and mitochondrial membranes, a localization that is maintained by retromer and the retromer-associated RAB7-specific GAP TBC1D5...
November 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29150658/differential-regulation-of-synaptic-ap-2-clathrin-vesicle-uncoating-in-synaptic-plasticity
#19
Ermes Candiello, Ratnakar Mishra, Bernhard Schmidt, Olaf Jahn, Peter Schu
AP-1/σ1B-deficiency causes X-linked intellectual disability. AP-1/σ1B -/- mice have impaired synaptic vesicle recycling, fewer synaptic vesicles and enhanced endosome maturation mediated by AP-1/σ1A. Despite defects in synaptic vesicle recycling synapses contain two times more endocytic AP-2 clathrin-coated vesicles. We demonstrate increased formation of two classes of AP-2/clathrin coated vesicles. One which uncoats readily and a second with a stabilised clathrin coat. Coat stabilisation is mediated by three molecular mechanisms: reduced recruitment of Hsc70 and synaptojanin1 and enhanced μ2/AP-2 phosphorylation and activation...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#20
Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson
The diversion of the membrane-bound β-secretase BACE1 from the endo-lysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the SNX4-mediated, signal independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the acidic cluster-dileucine DISLL cytoplasmic tail motif of BACE1...
November 15, 2017: Molecular Biology of the Cell
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