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Endocytic trafficking

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https://www.readbyqxmd.com/read/28424577/investigation-of-endocytic-pathways-for-the-internalization-of-exosome-associated-oligomeric-alpha-synuclein
#1
Marion Delenclos, Teodora Trendafilova, Divya Mahesh, Ann M Baine, Simon Moussaud, Irene K Yan, Tushar Patel, Pamela J McLean
Misfolding and aggregation of alpha-synuclein (αsyn) resulting in cytotoxicity is a hallmark of Parkinson's disease (PD) and related synucleinopathies. The recent body of evidence indicates that αsyn can be released from neuronal cells by nonconventional exocytosis involving extracellular vesicles (EVs) such as exosomes. The transfer of αsyn between cells has been proposed to be an important mechanism of disease propagation in PD. To date, exosome trafficking mechanisms, including release and cell-cell transmission, have not been fully described...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28422978/the-escrt-regulator-did2-maintains-the-balance-between-long-distance-endosomal-transport-and-endocytic-trafficking
#2
Carl Haag, Thomas Pohlmann, Michael Feldbrügge
In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes...
April 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28413120/endosome-to-trans-golgi-network-transport-of-proprotein-convertase-7-is-mediated-by-a-cluster-of-basic-amino-acids-and-palmitoylated-cysteines
#3
Jeroen Declercq, Bruno Ramos-Molina, Ragna Sannerud, Bas Brouwers, Vincent P E G Pruniau, Sandra Meulemans, Evelyn Plets, Wim Annaert, John W M Creemers
Proprotein Convertase 7 (PC7) is a Furin-like endoprotease that cleaves precursor proteins at basic amino acids. PC7 is concentrated in the trans-Golgi network (TGN) but it shuttles between the plasma membrane and the TGN depending on sequences in the cytoplasmic tail. A short region containing a three amino acids motif, P(724)-L(725)-C(726), is essential and sufficient for internalization of PC7 but not for TGN localization, which requires the additional presence of the juxtamembrane region. In this study we have investigated the contribution of a cluster of basic amino acids and two reversibly palmitoylated cysteine residues to endocytic trafficking...
April 7, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28411124/m3-muscarinic-acetylcholine-receptor-facilitates-the-endocytosis-of-mu-opioid-receptor-mediated-by-morphine-independently-of-the-formation-of-heteromeric-complexes
#4
Juan F Lopez-Gimenez, Elisa Alvarez-Curto, Graeme Milligan
Morphine inefficiency to induce the internalization of mu opioid (MOP) receptors observed in numerous experimental models constitutes a paradigm of G-protein coupled receptor (GPCR) functional selectivity. We recently described that activation of Gαq/11 proteins through 5-HT2A serotonin receptors co-expressed in the same cells facilitates MOP receptor endocytosis promoted by morphine. In order to explore whether a different Gαq/11 coupled GPCR would emulate this effect, a double stable Flp-In T-REx HEK293 cell line permanently expressing MOP-YFP receptors along with FLAG-M3-Cerulean receptors expressed in an inducible manner was generated...
April 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28406138/inhibition-of-endocytic-pathways-impacts-cytomegalovirus-maturation
#5
Madeline A Archer, Teal M Brechtel, Leslie E Davis, Rinkuben C Parmar, Mohammad H Hasan, Ritesh Tandon
Endocytic processes are critical for cellular entry of several viruses; however, the role of endocytosis in cellular trafficking of viruses beyond virus entry is only partially understood. Here, we utilized two laboratory strains (AD169 and Towne) of human cytomegalovirus (HCMV), which are known to use cell membrane fusion rather than endocytosis to enter fibroblasts, in order to study a post-entry role of endocytosis in HCMV life cycle. Upon pharmacological inhibition of dynamin-2 or clathrin terminal domain (TD) ligand association, these strains entered the cells successfully based on the expression of immediate early viral protein...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396666/dynamic-changes-in-the-intracellular-association-of-selected-rab-small-gtpases-with-mhc-class-ii-and-dm-during-dendritic-cell-maturation
#6
Gibrán Pérez-Montesinos, Orestes López-Ortega, Jessica Piedra-Reyes, Laura C Bonifaz, José Moreno
Antigen processing for presentation by major histocompatibility complex class II (MHCII) molecules requires the latter to travel through the endocytic pathway together with its chaperons: the invariant chain (Ii) and DM. Nevertheless, the nature of the compartments where MHCII molecules travel to acquire peptides lacks definition regarding molecules involved in intracellular vesicular trafficking, such as Rab small GTPases. We aimed to define which Rab proteins are present during the intracellular transport of MHCII, DM, and Ii through the endocytic pathway on their route to the cell surface during dendritic cell (DC) maturation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28395139/next-generation-precision-polyesters-enabling-optimization-of-ligand-receptor-stoichiometry-for-modular-drug-delivery
#7
Raghu Ganugula, Meenakshi Arora, Prabhjot Saini, Melissa Guada, Majeti N V Ravi Kumar
The success of receptor-mediated drug delivery primarily depends on the ability to optimize ligand-receptor stoichiometry. Conventional polyesters such as polylactide (PLA) or its copolymer, polylactide-co-glycolide (PLGA), do not allow such optimization due to their terminal functionality. We herein report the synthesis of 12 variations of the PLA-poly(ethylene glycol) (PEG) based precision-polyester (P2s) platform, permitting 5-12 periodically spaced carboxyl functional groups on the polymer backbone. These carboxyl groups were utilized to achieve variable degrees of gambogic acid (GA) conjugation to facilitate ligand-receptor stoichiometry optimization...
April 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28387218/retrograde-transport-of-trkb-containing-autophagosomes-via-the-adaptor-ap-2-mediates-neuronal-complexity-and-prevents-neurodegeneration
#8
Natalia L Kononenko, Gala A Claßen, Marijn Kuijpers, Dmytro Puchkov, Tanja Maritzen, Aleksandra Tempes, Anna R Malik, Agnieszka Skalecka, Sujoy Bera, Jacek Jaworski, Volker Haucke
Autophagosomes primarily mediate turnover of cytoplasmic proteins or organelles to provide nutrients and eliminate damaged proteins. In neurons, autophagosomes form in distal axons and are trafficked retrogradely to fuse with lysosomes in the soma. Although defective neuronal autophagy is associated with neurodegeneration, the function of neuronal autophagosomes remains incompletely understood. We show that in neurons, autophagosomes promote neuronal complexity and prevent neurodegeneration in vivo via retrograde transport of brain-derived neurotrophic factor (BDNF)-activated TrkB receptors...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28384198/tbc1d12-is-a-novel-rab11-binding-protein-that-modulates-neurite-outgrowth-of-pc12-cells
#9
Mai E Oguchi, Kenta Noguchi, Mitsunori Fukuda
Recycling endosomes are generally thought to play a central role in endocytic recycling, but recent evidence has indicated that they also participate in other cellular events, including cytokinesis, autophagy, and neurite outgrowth. Rab small GTPases are key regulators in membrane trafficking, and although several Rab isoforms, e.g., Rab11, have been shown to regulate recycling endosomal trafficking, the precise mechanism by which these Rabs regulate recycling endosomes is not fully understood. In this study, we focused on a Rab-GTPase-activating protein (Rab-GAP), one of the key regulators of Rabs, and comprehensively screened 43 mammalian Tre-2/Bub2/Cdc16 (TBC)/Rab-GAP-domain-containing proteins (TBC proteins) for proteins that specifically localize on recycling endosomes in mouse embryonic fibroblasts (MEFs)...
2017: PloS One
https://www.readbyqxmd.com/read/28381425/an-endosomal-syntaxin-and-the-ap-3-complex-are-required-for-formation-and-maturation-of-candidate-lysosome-related-secretory-organelles-mucocysts-in-tetrahymena-thermophila
#10
Harsimran Kaur, Daniela Sparvoli, Hiroko Osakada, Masaaki Iwamoto, Tokuko Haraguchi, Aaron P Turkewitz
The ciliate Tetrahymena thermophila synthesizes large secretory vesicles called mucocysts. Mucocyst biosynthesis shares features with dense core granules (DCGs) in animal cells, including proteolytic processing of cargo proteins during maturation. However, other molecular features have suggested relatedness to lysosome-related organelles (LROs). LROs, which include diverse organelles in animals, are formed via convergence of secretory and endocytic trafficking. Here we analyzed Tetrahymena Stx7l1p (syntaxin 7-like 1), a Qa SNARE whose homologs in other lineages are linked with vacuoles/LROs...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28379543/intra-endosomal-trafficking-mediated-by-lysobisphosphatidic-acid-contributes-to-intracellular-release-of-phosphorothioate-modified-antisense-oligonucleotides
#11
Shiyu Wang, Hong Sun, Michael Tanowitz, Xue-Hai Liang, Stanley T Crooke
Antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages are broadly used as research tools and therapeutic agents. Chemically modified PS-ASOs can mediate efficient target reduction by site-specific cleavage of RNA through RNase H1. PS-ASOs are known to be internalized via a number of endocytotic pathways and are released from membrane-enclosed endocytotic organelles, mainly late endosomes (LEs). This study was focused on the details of PS-ASO trafficking through endocytic pathways. It was found that lysobisphosphatidic acid (LBPA) is required for release of PS-ASOs from LEs...
April 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28377049/the-endocytic-pathways-of-a-secretory-granule-membrane-protein-in-hek293-cells-pam-and-egf-traverse-a-dynamic-multivesicular-body-network-together
#12
Nils Bäck, Kristiina Kanerva, Vishwanatha Kurutihalli, Andrew Yanik, Elina Ikonen, Richard E Mains, Betty A Eipper
Peptidylglycine α-amidating monooxygenase (PAM) is highly expressed in neurons and endocrine cells, where it catalyzes one of the final steps in the biosynthesis of bioactive peptides. PAM is also expressed in unicellular organisms such as Chlamydomonas reinhardtii, which do not store peptides in secretory granules. As for other granule membrane proteins, PAM is retrieved from the cell surface and returned to the trans-Golgi network. This pathway involves regulated entry of PAM into multivesicular body intralumenal vesicles (ILVs)...
March 28, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28368306/icam-1-binding-rhinoviruses-enter-hela-cells-via-multiple-pathways-and-travel-to-distinct-intracellular-compartments-for-uncoating
#13
Haleh Ganjian, Christin Zietz, Diana Mechtcheriakova, Dieter Blaas, Renate Fuchs
Of the more than 150 human rhinovirus (RV) serotypes, 89 utilize intercellular adhesion molecule-1 (ICAM-1) for cell entry. These belong either to species A or B. We recently demonstrated that RV-B14 and RV-A89, despite binding this same receptor, are routed into distinct endosomal compartments for release of their RNA into the cytosol. To gain insight into the underlying mechanism we now comparatively investigate the port of entry, temperature-dependence of uncoating, and intracellular routing of RV-B3, RV-B14, RV-A16, and RV-A89 in HeLa cells...
April 1, 2017: Viruses
https://www.readbyqxmd.com/read/28366874/impaired-vitreous-composition-and-retinal-pigment-epithelium-function-in-the-foxg1-lrp2-myopic-mice
#14
Olivier Cases, Antoine Obry, Sirine Ben-Yacoub, Sébastien Augustin, Antoine Joseph, Géraldine Toutirais, Manuel Simonutti, Annabel Christ, Pascal Cosette, Renata Kozyraki
High myopia (HM) is one of the main causes of visual impairment and blindness all over the world and an unsolved medical problem. Persons with HM are predisposed to other eye pathologies such as retinal detachment, myopic retinopathy or glaucomatous optic neuropathy, complications that may at least partly result from the extensive liquefaction of the myopic vitreous gel. To identify the involvement of the liquid vitreous in the pathogenesis of HM we here analyzed the vitreous of the recently described highly myopic low density lipoprotein receptor-related protein 2 (Lrp2)-deficient eyes...
March 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28362242/arf-gaps-a-family-of-proteins-with-disparate-functions-that-converge-on-a-common-structure-the-integrin-adhesion-complex
#15
Teresa Vitali, Sofia Girald-Berlingeri, Paul A Randazzo, Pei-Wen Chen
ADP-ribosylation factors (Arfs) are members of the Ras GTPase superfamily. The function of Arfs is dependent on GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. Arf GAPs have been shown to be present in integrin adhesion complexes, which include focal adhesions. Integrin adhesion complexes are composed of integrins, scaffolding proteins and signaling proteins and regulate cell proliferation, survival, differentiation and migration...
March 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/28360834/an-aberrant-phosphorylation-of-amyloid-precursor-protein-tyrosine-regulates-its-trafficking-and-the-binding-to-the-clathrin-endocytic-complex-in-neural-stem-cells-of-alzheimer-s-disease-patients
#16
Ebbe T Poulsen, Filomena Iannuzzi, Helle F Rasmussen, Thorsten J Maier, Jan J Enghild, Arne L Jørgensen, Carmela Matrone
Alzheimer's disease (AD) is the most common cause of dementia and is likely caused by defective amyloid precursor protein (APP) trafficking and processing in neurons leading to amyloid plaques containing the amyloid-β (Aβ) APP peptide byproducts. Understanding how APP is targeted to selected destinations inside neurons and identifying the mechanisms responsible for the generation of Aβ are thus the keys for the advancement of new therapies. We previously developed a mouse model with a mutation at tyrosine (Tyr) 682 in the C-terminus of APP...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28356223/the-role-of-the-pi-3-5-p2-kinase-tbfab1-in-endo-lysosomal-trafficking-in-trypanosoma-brucei
#17
Julia K Gilden, Khan Umaer, Emilia K Kruzel, Oliver Hecht, Renan O Correa, John M Mansfield, James D Bangs
Protein trafficking through endo/lysosomal compartments is critically important to the biology of the protozoan parasite Trypanosoma brucei, but the routes material may take to the lysosome, as well as the molecular factors regulating those routes, remain incompletely understood. Phosphoinositides are signaling phospholipids that regulate many trafficking events by recruiting specific effector proteins to discrete membrane subdomains. In this study, we investigate the role of one phosphoinositide, PI(3,5)P2 in T...
March 27, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28349933/the-vps4-component-of-the-escrt-machinery-plays-an-essential-role-in-hpv-infectious-entry-and-capsid-disassembly
#18
Justyna Broniarczyk, David Pim, Paola Massimi, Martina Bergant, Anna Goździcka-Józefiak, Colin Crump, Lawrence Banks
Human Papillomavirus (HPV) infection involves multiple steps, from cell attachment, through endocytic trafficking towards the trans-Golgi network, and, ultimately, the entry into the nucleus during mitosis. An essential viral protein in infectious entry is the minor capsid protein L2, which engages different components of the endocytic sorting machinery during this process. The ESCRT machinery is one such component that seems to play an important role in the early stages of infection. Here we have analysed the role of specific ESCRT components in HPV infection, and we find an essential role for VPS4...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28349644/changes-to-cholesterol-trafficking-in-macrophages-by-leishmania-parasites-infection
#19
Geo Semini, Daniel Paape, Athina Paterou, Juliane Schroeder, Martin Barrios-Llerena, Toni Aebischer
Leishmania spp. are protozoan parasites that are transmitted by sandfly vectors during blood sucking to vertebrate hosts and cause a spectrum of diseases called leishmaniases. It has been demonstrated that host cholesterol plays an important role during Leishmania infection. Nevertheless, little is known about the intracellular distribution of this lipid early after internalization of the parasite. Here, pulse-chase experiments with radiolabeled cholesteryl esterified to fatty acids bound to low-density lipoproteins indicated that retention of this source of cholesterol is increased in parasite-containing subcellular fractions, while uptake is unaffected...
March 27, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28349243/endocytic-trafficking-of-hiv-gp120-is-mediated-by-dynamin-and-plays-a-role-in-gp120-neurotoxicity
#20
Erin D Wenzel, Alessia Bachis, Valeria Avdoshina, Francesca Taraballi, Ennio Tasciotti, Italo Mocchetti
Neurons that endocytose the human immunodeficiency virus-1 (HIV) protein gp120 exhibit neurite retraction and activation of caspase-3, suggesting that the endocytic process may be crucial for gp120-mediated neuronal injury. The goal of this study is to demonstrate that internalization and accumulation of gp120 play a role in its neurotoxic effects. In mammalian cells, endocytosis is primarily a dynamin-dependent process. To establish whether gp120 is endocytosed in a dynamin-dependent manner, we used fibroblasts in which deletion of dynamins was induced by tamoxifen...
March 27, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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