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Endosomal trafficking

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https://www.readbyqxmd.com/read/29776664/rhod-localization-and-function-is-dependent-on-its-gtp-gdp-bound-state-and-unique-n-terminal-motif
#1
Magdalena Blom, Katarina Reis, Pontus Aspenström
The atypical Rho GTPase RhoD has previously been shown to have a major impact on the organization and function of the actin filament system. However, when first discovered, RhoD was found to regulate endosome trafficking and dynamics and we therefore sought to investigate this regulation in more detail. We found that exogenously expressed RhoD in human fibroblasts localized to vesicles and the plasma membrane and that the active GTP-bound conformation was required for the plasma membrane localization but not for vesicle localization...
May 16, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29776606/advances-in-membrane-trafficking-and-endosomal-signaling-of-g-protein-coupled-receptors
#2
Aylin C Hanyaloglu
The integration of GPCR signaling with membrane trafficking, as a single orchestrated system, is a theme increasingly evident with the growing reports of GPCR endosomal signaling. Once viewed as a mechanism to regulate cell surface heterotrimeric G protein signaling, the endocytic trafficking system is complex, highly compartmentalized, yet deeply interconnected with cell signaling. The organization of receptors into distinct plasma membrane signalosomes, biochemically distinct endosomal populations, endosomal microdomains, and its communication with distinct subcellular organelles such as the Golgi provides multiple unique signaling platforms that are critical for specifying receptor function physiologically and pathophysiologically...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29769350/rab5-rab7-and-rab11-are-required-for-caveolae-dependent-endocytosis-of-classic-swine-fever-virus-in-porcine-alveolar-macrophages
#3
Yun-Na Zhang, Ya-Yun Liu, Fu-Chuan Xiao, Chun-Chun Liu, Xiao-Dong Liang, Jing Chen, Jing Zhou, Abdul Sattar Baloch, Lin Kan, Bin Zhou, Hua-Ji Qiu
The members of Flaviviridae utilize several endocytic pathways to enter a variety of host cells. Our previous work showed that classical swine fever virus (CSFV) enters porcine kidney (PK-15) cells through a clathrin-dependent pathway that requires Rab5 and Rab7. The entry mechanism for CSFV into other cell lines remains unclear, for instance, porcine alveolar macrophages (3D4/21 cells). More importantly, the trafficking of CSFV within endosomes controlled by Rab GTPases is unknown in 3D4/21 cells. In this study, entry and post-internalization of CSFV were analyzed using chemical inhibitors, RNA interference, and dominant negative (DN) mutants...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29768176/the-chaperone-unc93b1-regulates-toll-like-receptor-stability-independently-of-endosomal-tlr-transport
#4
Karin Pelka, Damien Bertheloot, Elisa Reimer, Kshiti Phulphagar, Susanne V Schmidt, Anette Christ, Rainer Stahl, Nicki Watson, Kensuke Miyake, Nir Hacohen, Albert Haas, Melanie M Brinkmann, Ann Marshak-Rothstein, Felix Meissner, Eicke Latz
Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling compartments and to guide the flagellin receptor TLR5 to the cell surface, raising the question of how UNC93B1 mediates differential TLR trafficking. Here, we report that UNC93B1 regulates a step upstream of the differential TLR trafficking process...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29761602/vmp1-marks-er-subdomains-enriched-in-phospholipid-synthesizing-enzymes-and-is-required-for-phosphoinositide-distribution
#5
Luis-Carlos Tábara, Juan-Jesús Vicente, Joanna Biazik, Eeva-Liisa Eskelinen, Olivier Vincent, Ricardo Escalante
The multispanning membrane protein VMP1 (Vacuole membrane protein 1) marks and regulates endoplasmic reticulum (ER)-domains associated with diverse ER-organelle membrane contact sites (MCSs). A proportion of these domains associate with endosomes during their maturation and remodeling. We found that these VMP1-domains are enriched in CEPT1 and PIS1, two ER enzymes required for the synthesis of various phospholipids. Interestingly, the lack of VMP1 impairs the formation of PIS1-enriched ER domains, suggesting a role in the distribution of phosphoinositides...
May 14, 2018: Traffic
https://www.readbyqxmd.com/read/29757220/annexins-coordinators-of-cholesterol-homeostasis-in-endocytic-pathways
#6
REVIEW
Carles Rentero, Patricia Blanco-Muñoz, Elsa Meneses-Salas, Thomas Grewal, Carlos Enrich
The spatiotemporal regulation of calcium (Ca2+ ) storage in late endosomes (LE) and lysosomes (Lys) is increasingly recognized to influence a variety of membrane trafficking events, including endocytosis, exocytosis, and autophagy. Alterations in Ca2+ homeostasis within the LE/Lys compartment are implicated in human diseases, ranging from lysosomal storage diseases (LSDs) to neurodegeneration and cancer, and they correlate with changes in the membrane binding behaviour of Ca2+ -binding proteins. This also includes Annexins (AnxA), which is a family of Ca2+ -binding proteins participating in membrane traffic and tethering, microdomain organization, cytoskeleton interactions, Ca2+ signalling, and LE/Lys positioning...
May 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29755461/efficient-uptake-of-recombinant-lipidated-survivin-by-antigen-presenting-cells-initiates-antigen-cross-presentation-and-antitumor-immunity
#7
Chen-Yi Chiang, Yi-Jyun Chen, Chiao-Chieh Wu, Shih-Jen Liu, Chih-Hsiang Leng, Hsin-Wei Chen
Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their toll-like receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli -based system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755290/retromer-dysfunction-and-neurodegenerative-disease
#8
REVIEW
Christiane Reitz
In recent years, genomic, animal and cell biology studies have implicated deficiencies in retromer-mediated trafficking of proteins in an increasing number of neurodegenerative diseases including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Frontotemporal Lobar Degener-ation (FTLD). The retromer complex, which is highly conserved across all eukaryotes, regulates the sorting of transmembrane proteins out of endo-somes to the cell surface or to the trans-Golgi network. Within retromer, cargo selection and binding are performed by a trimer of the Vps26, Vps29 and Vps35 proteins, named the "Cargo-Selective Complex (CSC)"...
May 2018: Current Genomics
https://www.readbyqxmd.com/read/29749929/integration-of-two-rab5-groups-during-endosomal-transport-in-plants
#9
Emi Ito, Kazuo Ebine, Seung-Won Choi, Sakura Ichinose, Tomohiro Uemura, Akihiko Nakano, Takashi Ueda
RAB5 is a key regulator of endosomal functions in eukaryotic cells. Plants possess two different RAB5 groups, canonical and plant-unique types, which act via unknown counteracting mechanisms. Here, we identified an effector molecule of the plant-unique RAB5 in Arabidopsis thaliana , ARA6, which we designated PLANT-UNIQUE RAB5 EFFECTOR 2 (PUF2). Preferential colocalization with canonical RAB5 on endosomes and genetic interaction analysis indicated that PUF2 coordinates vacuolar transport with canonical RAB5, although PUF2 was identified as an effector of ARA6...
May 11, 2018: ELife
https://www.readbyqxmd.com/read/29749721/characterization-of-novel-piperidine-based-inhibitor-of-cathepsin-b-dependent-bacterial-toxins-and-viruses
#10
Stella Hartmann, Renae Lopez Cruz, Saleem Alameh, Chi-Lee C Ho, Amy Rabideau, Bradley L Pentelute, Kenneth A Bradley, Mikhail Martchenko
Exploiting the host endocytic trafficking pathway is a common mechanism by which bacterial exotoxins gain entry to exert virulent effects upon the host cells. A previous study identified a small-molecule, 1-(2,6-dimethyl-1-piperidinyl)-3-[(2-isopropyl-5-methylcyclohexyl)oxy]-2-propanol, that blocks the process of anthrax lethal toxin (LT) cytotoxicity. Here, we report the characterization of the bioactivity of this compound, which we named RC1. We found that RC1 protected host cells independently of LT concentration and also blocked intoxication by other bacterial exotoxins, suggesting that the target of the compound is a host factor...
May 18, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29748997/the-recycling-endosome-and-bacterial-pathogens
#11
REVIEW
Samual C Allgood, M Ramona Neunuebel
Bacterial pathogens have developed a wide range of strategies to survive within human cells. A number of pathogens multiply in a vacuolar compartment, while others can rupture the vacuole and replicate in the host cytosol. A common theme among many bacterial pathogens is the use of specialized secretion systems to deliver effector proteins into the host cell. These effectors can manipulate the host's membrane trafficking pathways to remodel the vacuole into a replication-permissive niche and prevent degradation...
May 10, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29748898/cystatin-f-as-a-regulator-of-immune-cell-cytotoxicity
#12
REVIEW
Janko Kos, Milica Perišić Nanut, Mateja Prunk, Jerica Sabotič, Esmeralda Dautović, Anahid Jewett
Cysteine cathepsins are lysosomal peptidases involved in the regulation of innate and adaptive immune responses. Among the diverse processes, regulation of granule-dependent cytotoxicity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells during cancer progression has recently gained significant attention. The function of cysteine cathepsins is regulated by endogenous cysteine protease inhibitors-cystatins. Whereas other cystatins are generally cytosolic or extracellular proteins, cystatin F is present in endosomes and lysosomes and is thus able to regulate the activity of its target directly...
May 10, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29746785/from-hitchhiker-to-hijacker-pathogen-exploitation-of-endosomal-phosphoinositides
#13
Shirley Qiu, Marceline Côté
Signalling through phosphoinositide lipids is essential for regulating many cellular processes, including endosomal trafficking. A number of intracellular pathogens have found ways to subvert host trafficking pathways via exploitation of endosomal phosphoinositides. This review will discuss how pathogens such as bacteria, viruses, and eukaryotic parasites depend on endosomal phosphoinositides for infection, as well as the mechanisms through which some are able to actively manipulate these signalling lipids to facilitate invasion, survival, replication, and immune evasion...
May 10, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29738458/the-annexin-a1-receptor-fpr2-regulates-the-endosomal-export-of-influenza-virus
#14
Fryad Rahman, Mohammad Chebbo, Noémie Courtin, Aurelien Fotso Fotso, Marie-Christine Alessi, Béatrice Riteau
The Formyl Peptide Receptor 2 (FPR2) is a novel promising target for the treatment of influenza. During viral infection, FPR2 is activated by annexinA1, which is present in the envelope of influenza viruses; this activation promotes virus replication. Here, we investigated whether blockage of FPR2 would affect the genome trafficking of influenza virus. We found that, upon infection and cell treatment with the specific FPR2 antagonist WRW4 or the anti-FPR2 monoclonal antibody, FN-1D6-AI, influenza viruses were blocked into endosomes...
May 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29738095/toxoplasma-gondii-tfp1-is-an-essential-transporter-family-protein-critical-for-microneme-maturation-and-exocytosis
#15
Pierre-Mehdi Hammoudi, Bohumil Maco, Sunil Kumar Dogga, Karine Frénal, Dominique Soldati-Favre
Invasion and egress are two key steps in the lytic cycle of Apicomplexa that are governed by the sequential discharge of proteins from two apical secretory organelles called micronemes and rhoptries. In Toxoplasma gondii, the biogenesis of these specialized organelles depends on the post Golgi trafficking machinery, forming an endosomal-like compartment (ELC) resembling endomembrane systems found in eukaryotes. In this study, we have characterized four phylogenetically related Transporter Facilitator Proteins (TFPs) conserved among the apicomplexans...
May 8, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29724910/retromer-associates-with-the-cytoplasmic-amino-terminus-of-polycystin-2
#16
Frances C Tilley, Matthew Gallon, Chong Luo, Chris M Danson, Jing Zhou, Peter J Cullen
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic human disease, with around 12.5 million people affected worldwide. ADPKD results from mutations in either PKD1 or PKD2 , which encode the atypical G-protein coupled receptor polycystin-1 (PC1) and the transient receptor potential channel polycystin-2 (PC2) respectively. Although altered intracellular trafficking of PC1 and PC2 appear as an underlying feature of ADPKD, the mechanisms which govern vesicular transport of the polycystins through the biosynthetic and endosomal membrane networks remain to be fully elucidated...
May 3, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29724789/ligand-specific-signaling-profiles-and-resensitization-mechanisms-of-the-neuromedin-u2-receptor
#17
Khaled Alhosaini, Omar Bahattab, Heider Qassam, John Challiss, Gary B Willars
The structurally related, but distinct neuropeptides, neuromedin U (NmU) and neuromedin S (NmS) are ligands of two G protein-coupled NmU receptors (NMU1, NMU2). Hypothalamic NMU2 regulates feeding behavior and energy expenditure and has therapeutic potential as an anti-obesity target, making an understanding of its signaling and regulation of particular interest. NMU2 binds both NmU and NmS with high affinity, resulting in receptor-ligand co-internalization. We have investigated whether receptor trafficking events post-internalization are 'biased' by the ligand bound and can therefore influence signaling function...
May 3, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29722136/phospho-regulation-of-intrinsically-disordered-proteins-for-actin-assembly-and-endocytosis
#18
Yansong Miao, Teepiyanut Tipakornsaowapak, Liangzhen Zheng, Yuguang Mu, Eric Lewellyn
Actin filament assembly contributes to the endocytic pathway pleiotropically, with active roles in clathrin-dependent and clathrin-independent endocytosis as well as subsequent endosomal trafficking. Endocytosis comprises a series of dynamic events, including the initiation of membrane curvature, bud invagination, vesicle abscission, and subsequent vesicular transport. The ultimate success of endocytosis requires the coordinated activities of proteins that trigger actin polymerization, recruit actin-binding proteins (ABPs), and organize endocytic proteins (EPs) that promote membrane curvature through molecular crowding or scaffolding mechanisms...
May 2, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29720392/activation-of-self-incompatibility-signaling-in-transgenic-arabidopsis-thaliana-is-independent-of-ap2-based-clathrin-mediated-endocytosis
#19
Masaya Yamamoto, Takeshi Nishio, June B Nasrallah
Internalization of plasma membrane (PM)-localized ligand-activated receptor kinases and their trafficking to sorting endosomes have traditionally been viewed as functioning primarily in the down-regulation of receptor signaling, but are now considered to be also essential for signaling by some receptors. A major mechanism for internalization of PM proteins is clathrin-mediated endocytosis (CME). CME is mediated by the Adaptor Protein Complex 2 (AP2), which is involved in interaction of the AP2 μ-adaptin subunit with a tyrosine-based Yxxφ motif located in the cytoplasmic domain of the cargo protein...
May 2, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29717057/to-be-or-not-to-be-secreted-as-exosomes-a-balance-finely-tuned-by-the-mechanisms-of-biogenesis
#20
REVIEW
Roberta Palmulli, Guillaume van Niel
The release of extracellular vesicles such as exosomes provides an attractive intercellular communication pathway. Exosomes are 30- to 150-nm membrane vesicles that are generated in endosomal compartment and act as intercellular mediators in both physiological and pathological context. Despite the growing interest in exosome functions, the mechanisms responsible for their biogenesis and secretion are still not completely understood. Knowledge about these mechanisms is important because they control the composition, and hence the function and secretion, of exosomes...
May 1, 2018: Essays in Biochemistry
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