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Recycling endosome

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https://www.readbyqxmd.com/read/29028801/docrl-maintains-immune-cell-quiescence-by-regulating-endosomal-traffic
#1
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/29021338/a-daple-akt-feed-forward-loop-enhances-non-canonical-wnt-signals-by-compartmentalizing-%C3%AE-catenin
#2
Nicolas Aznar, Nina Sun, Ying Dunkel, Jason Ear, Matthew D Buschman, Pradipta Ghosh
Cellular proliferation is antagonistically regulated by canonical and non-canonical Wnt signals; their dysbalance triggers cancers. We previously showed that a multimodular signal transducer, Daple, enhances PI3-K→Akt signals within the non-canonical Wnt signaling pathway and antagonistically inhibits canonical Wnt responses. Here we demonstrate that the PI3-K→Akt pathway serves as a positive feedback loop that further enhances non-canonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide(PI)-binding domain of Daple, Akt abolishes Daple's ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs)...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28979185/the-membrane-glycoprotein-m6a-endocytic-recycling-pathway-involves-clathrin-mediated-endocytosis-and-affects-neuronal-synapses
#3
Micaela D Garcia, Karina Formoso, Gabriela I Aparicio, Alberto C C Frasch, Camila Scorticati
Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28976518/a-novel-type-of-quantum-dot-transferrin-conjugate-using-dna-hybridization-mimics-intracellular-recycling-of-endogenous-transferrin
#4
Anusuya Banerjee, Chloé Grazon, Thomas Pons, Dhiraj Bhatia, Cesar Augusto Valades-Cruz, Ludger Johannes, Yamuna Krishnan, Benoit Dubertret
Colloidal nanoparticles such as Quantum Dots (QDs) are promising alternatives to organic fluorophores, especially for long duration bioimaging. For specific targeting applications, QDs frequently require functionalization with selected proteins. In this regard, conjugation of proteins to QDs such that the nanobioconjugates retain the endogenous behavior of the coupled protein remains challenging. We have developed a novel method to conjugate a protein, transferrin (Tf), to QDs using DNA hybridization. These conjugates are characterized biochemically, and the trafficking properties in live cells are investigated...
October 4, 2017: Nanoscale
https://www.readbyqxmd.com/read/28972156/preferential-association-with-clc-3-permits-sorting-of-clc-4-into-endosomal-compartments
#5
Raul E Guzman, Stefanie Bungert-Plümke, Arne Franzen, Christoph Fahlke
ClC-4 is an intracellular Cl(-)-H(+) exchanger, which is highly expressed in the brain and whose dysfunction has been linked to intellectual disability and epilepsy. We here studied the subcellular localization of human ClC-4 in heterologous expression systems. ClC-4 is retained in the endoplasmic reticulum (ER) upon overexpression in HEK293T cells. Co-expression with distinct ClC-3 splice variants targets ClC-4 to late endosome/lysosomes (ClC-3a and ClC-3b), recycling endosome (ClC-3c) or to the Golgi (ClC-3e)...
September 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28967944/computational-approaches-for-deciphering-the-equilibrium-and-kinetic-properties-of-iron-transport-proteins
#6
REVIEW
H Abdizadeh, A R Atilgan, C Atilgan, B Dedeoglu
With the advances in three-dimensional structure determination techniques, high quality structures of the iron transport proteins transferrin and the bacterial ferric binding protein (FbpA) have been deposited in the past decade. These are proteins of relatively large size, and developments in hardware and software have only recently made it possible to study their dynamics using standard computational resources. We review computational techniques towards understanding the equilibrium and kinetic properties of iron transport proteins under different environmental conditions...
October 2, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28960203/retriever-fetches-integrins-from-endosomes
#7
Catherine Rabouille
Recycling from endosomes to the plasma membrane is an important step in cell homeostasis. The retromer/SNX27/WASH complex recycles numerous receptors, but key ones are still unaccounted for. Now a related conserved heterotrimer, called retriever, has been identified that, together with SNX17, the CCC complex and WASH, mediates the recycling of α5β1 integrins.
September 29, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28951093/thioether-stapled-macrocyclic-inhibitors-of-the-eh-domain-of-ehd1
#8
Alissa J Kamens, Kaley M Mientkiewicz, Robyn J Eisert, Jenna A Walz, Charles R Mace, Joshua A Kritzer
Recycling of receptors from the endosomal recycling compartment to the plasma membrane is a critical cellular process, and recycling is particularly important for maintaining invasiveness in solid tumors. In this work, we continue our efforts to inhibit EHD1, a critical adaptor protein involved in receptor recycling. We applied a diversity-oriented macrocyclization approach to produce cyclic peptides with varied conformations, but that each contain a motif that binds to the EH domain of EHD1. Screening these uncovered several new inhibitors for EHD1's EH domain, the most potent of which bound with a Kd of 3...
September 18, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28945820/anthrax-edema-toxin-disrupts-distinct-steps-in-rab11-dependent-junctional-transport
#9
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/28937584/targeted-delivery-of-sirna-with-ph-responsive-hybrid-gold-nanostars-for-cancer-treatment
#10
Hongyan Zhu, Wanwan Liu, Ziting Cheng, Ke Yao, Yu Yang, Bohui Xu, Gaoxing Su
In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose (DG) is the targeting molecule, polyethylene glycol (PEG) helps to improve the dispersity and biocompatibility, 9-poly-d-arginine (9R) is employed to provide a positive surface charge and adsorb negative siRNA, and hydrazone bonds are pH-responsive and can avoid receptor-mediated endosomal recycling...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28935633/sequence-dependent-cargo-recognition-by-snx-bars-mediates-retromer-independent-transport-of-ci-mpr
#11
Boris Simonetti, Chris M Danson, Kate J Heesom, Peter J Cullen
Endosomal recycling of transmembrane proteins requires sequence-dependent recognition of motifs present within their intracellular cytosolic domains. In this study, we have reexamined the role of retromer in the sequence-dependent endosome-to-trans-Golgi network (TGN) transport of the cation-independent mannose 6-phosphate receptor (CI-MPR). Although the knockdown or knockout of retromer does not perturb CI-MPR transport, the targeting of the retromer-linked sorting nexin (SNX)-Bin, Amphiphysin, and Rvs (BAR) proteins leads to a pronounced defect in CI-MPR endosome-to-TGN transport...
September 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28935632/cargo-selective-snx-bar-proteins-mediate-retromer-trimer-independent-retrograde-transport
#12
Arunas Kvainickas, Ana Jimenez-Orgaz, Heike Nägele, Zehan Hu, Jörn Dengjel, Florian Steinberg
The retromer complex, which recycles the cation-independent mannose 6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), is thought to consist of a cargo-selective VPS26-VPS29-VPS35 trimer and a membrane-deforming subunit of sorting nexin (SNX)-Bin, Amphyphysin, and Rvs (BAR; SNX-BAR) proteins. In this study, we demonstrate that heterodimers of the SNX-BAR proteins, SNX1, SNX2, SNX5, and SNX6, are the cargo-selective elements that mediate the retrograde transport of CI-MPR from endosomes to the TGN independently of the core retromer trimer...
September 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28926616/co-ordinated-activation-of-classical-and-novel-pkc-isoforms-is-required-for-pma-induced-mtorc1-activation
#13
Mengling Liu, Christopher J Clarke, Mohamed F Salama, Yeon Ja Choi, Lina M Obeid, Yusuf A Hannun
Protein kinase C (PKC) has been shown to activate the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, a central hub in the regulation of cell metabolism, growth and proliferation. However, the mechanisms by which PKCs activate mTORC1 are still ambiguous. Our previous study revealed that activation of classical PKCs (cPKC) results in the perinuclear accumulation of cPKC and phospholipase D2 (PLD2) in recycling endosomes in a PLD2-dependent manner. Here, we report that mTORC1 activation by phorbol 12,13-myristate acetate (PMA) requires both classic, cPKC, and novel PKC (nPKC) isoforms, specifically PKCη, acting through distinct pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28922401/rab11-family-expression-in-the-human-placenta-localization-at-the-maternal-fetal-interface
#14
Elizabeth S Taglauer, Patrycja A Artemiuk, Sara R Hanscom, Andrew J Lindsay, Danielle Wuebbolt, Fionnuala M Breathnach, Elizabeth C Tully, Amir R Khan, Mary W McCaffrey
Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28910396/pi3k-c2%C3%AE-knockdown-decreases-autophagy-and-maturation-of-endocytic-vesicles
#15
Nathan M Merrill, Joshua L Schipper, Jonathan B Karnes, Audra L Kauffman, Katie R Martin, Jeffrey P MacKeigan
Phosphoinositide 3-kinase (PI3K) family members are involved in diverse cellular fates including cell growth, proliferation, and survival. While many molecular details are known about the Class I and III PI3Ks, less is known about the Class II PI3Ks. To explore the function of all eight PI3K isoforms in autophagy, we knock down each gene individually and measure autophagy. We find a significant decrease in autophagy following siRNA-mediated PIK3C2A (encoding the Class 2 PI3K, PI3K-C2α) knockdown. This defective autophagy is rescued by exogenous PI3K-C2α, but not kinase-dead PI3K-C2α...
2017: PloS One
https://www.readbyqxmd.com/read/28902870/reduced%C3%A2-insulin-signaling-maintains-electrical-transmission-in-a-neural-circuit-in-aging-flies
#16
Hrvoje Augustin, Kieran McGourty, Marcus J Allen, Sirisha Kudumala Madem, Jennifer Adcott, Fiona Kerr, Chi Tung Wong, Alec Vincent, Tanja Godenschwege, Emmanuel Boucrot, Linda Partridge
Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the "insulin paradox"). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced...
September 2017: PLoS Biology
https://www.readbyqxmd.com/read/28892079/retriever-is-a-multiprotein-complex-for-retromer-independent-endosomal-cargo-recycling
#17
Kerrie E McNally, Rebecca Faulkner, Florian Steinberg, Matthew Gallon, Rajesh Ghai, David Pim, Paul Langton, Neil Pearson, Chris M Danson, Heike Nägele, Lindsey L Morris, Amika Singla, Brittany L Overlee, Kate J Heesom, Richard Sessions, Lawrence Banks, Brett M Collins, Imre Berger, Daniel D Billadeau, Ezra Burstein, Peter J Cullen
Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer...
September 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28878020/lipid-stress-inhibits-endocytosis-of-melanocortin-4-receptor-from-modified-clathrin-enriched-sites-and-impairs-receptor-desensitization
#18
Kimberly A Cooney, Brent M Molden, Nicholas S Kowalczyk, Susan Russell, Giulia Baldini
Melanocortin-4 receptor (MC4R) is a G protein coupled receptor expressed in the brain hypothalamus where it regulates energy homeostasis. MC4R agonists function to lower food intake and weight. In this respect, while obesity promotes hyperlipidemia and hypothalamic injury, MC4R agonists are nevertheless more effective to reduce food intake within hours of administration in overweight, rather than lean, mice. MC4R undergoes constitutive internalization and recycling to the plasma membrane, with agonist binding inducing receptor retention along the intracellular route and, under prolonged exposure, desensitization...
September 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28875935/golgi-independent-secretory-trafficking-through-recycling-endosomes-in-neuronal-dendrites-and-spines
#19
Aaron B Bowen, Ashley M Bourke, Brian G Hiester, Cyril Hanus, Matthew J Kennedy
Neurons face the challenge of regulating the abundance, distribution and repertoire of integral membrane proteins within their immense, architecturally complex dendritic arbors. While the endoplasmic reticulum (ER) supports dendritic translation, most dendrites lack the Golgi apparatus (GA), an essential organelle for conventional secretory trafficking. Thus, whether secretory cargo is locally trafficked in dendrites through a non-canonical pathway remains a fundamental question. Here we define the dendritic trafficking itinerary for key synaptic molecules in rat cortical neurons...
September 6, 2017: ELife
https://www.readbyqxmd.com/read/28874679/the-endosomal-neuronal-proteins-nsg1-neep21-and-nsg2-p19-are-itinerant-not-resident-proteins-of-dendritic-endosomes
#20
Chan Choo Yap, Laura Digilio, Lloyd McMahon, Bettina Winckler
Membrane traffic critically regulates most aspects of neuronal function. Neurons express many neuronal-specific proteins that regulate membrane traffic, including the poorly understood small transmembrane proteins neural-specific gene 1 and 2 (Nsg1/NEEP21 and Nsg2/P19). Nsg1 has been implicated in regulating endosomal recycling and sorting of several important neuronal receptors. Nsg2 is largely unstudied. At steady-state, Nsg1 and Nsg2 only partially co-localize with known endosomal compartments, and it was suggested that they mark a neuronal-specific endosome...
September 5, 2017: Scientific Reports
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