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https://www.readbyqxmd.com/read/29150640/early-endosome-motility-mediates-%C3%AE-amylase-production-and-cell-differentiation-in-aspergillus-oryzae
#1
Yusuke Togo, Yujiro Higuchi, Yoshinori Katakura, Kaoru Takegawa
Recent research in filamentous fungi has revealed that the motility of an endocytic organelle early endosome (EE) has a versatile role in many physiological functions. Here, to further examine the motility of EEs in the industrially important fungus Aspergillus oryzae, we visualized these organelles via the Rab5 homolog AoRab5 and identified AoHok1, a putative linker protein between an EE and a motor protein. The Aohok1 disruptant showed retarded mycelial growth and no EE motility, in addition to an apical accumulation of EEs and peroxisomes...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127297/rab5-is-critical-for-snap23-regulated-granule-granule-fusion-during-compound-exocytosis
#2
Ofir Klein, Amit Roded, Neta Zur, Nurit P Azouz, Olga Pasternak, Koret Hirschberg, Ilan Hammel, Paul A Roche, Ayaka Yatsu, Mitsunori Fukuda, Stephen J Galli, Ronit Sagi-Eisenberg
Compound exocytosis is considered the most massive mode of exocytosis, during which the membranes of secretory granules (SGs) fuse with each other to form a channel through which the entire contents of their granules is released. The underlying mechanisms of compound exocytosis remain largely unresolved. Here we show that the small GTPase Rab5, a known regulator of endocytosis, is pivotal for compound exocytosis in mast cells. Silencing of Rab5 shifts receptor-triggered secretion from a compound to a full exocytosis mode, in which SGs individually fuse with the plasma membrane...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117102/mechanisms-of-entry-and-endosomal-pathway-of-african-swine-fever-virus
#3
REVIEW
Elena G. Sánchez, Daniel Pérez-Núñez, Yolanda Revilla
African Swine Fever Virus (ASFV) causes a serious swine disease that is endemic in Africa and Sardinia and presently spreading in Russia and neighboring countries, including Poland and recently, the Czech Republic. This uncontrolled dissemination is a world-wide threat, as no specific protection or vaccine is available. ASFV is a very complex icosahedral, enveloped virus about 200 nm in diameter, which infects several members of pigs. The virus enters host cells by receptor-mediated endocytosis that depends on energy, vacuolar pH and temperature...
November 8, 2017: Vaccines
https://www.readbyqxmd.com/read/29099266/calpain2-mediates-rab5-driven-focal-adhesion-disassembly-and-cell-migration
#4
Pablo A Mendoza, Patricio Silva, Jorge Díaz, Cecilia Arriagada, Jimena Canales, Oscar Cerda, Vicente A Torres
The early endosome protein Rab5 was recently shown to promote cell migration by enhancing focal adhesion disassembly through mechanisms that remain elusive. Focal adhesion disassembly is associated to proteolysis of talin, in a process that requires calpain2. Since calpain2 has been found at vesicles and endosomal compartments, we hypothesized that Rab5 stimulates calpain2 activity, leading to enhanced focal adhesion disassembly in migrating cells. We observed that calpain2 co-localizes with EEA1-positive early endosomes and co-immunoprecipitate with EEA1 and Rab5 in A549 lung carcinoma cells undergoing spreading, whereas Rab5 knock-down decreased the accumulation of calpain2 at early endosomal-enriched fractions...
November 3, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29095572/structural-plasticity-mediates-distinct-gap-dependent-gtp-hydrolysis-mechanisms-in-rab33-and-rab5
#5
Soneya Majumdar, Abhishek Acharya, Balaji Prakash
The classical GTP hydrolysis mechanism, as seen in Ras, employs a catalytic Gln, provided in-cis by the GTPase, and an Arginine supplied in-trans by a GTPase Activating Protein (GAP). The key idea emergent from a large body of research on small GTPases is that GTPases employ a variety of different hydrolysis mechanisms; evidently, these variations permit diverse rates of GTPase inactivation, crucial for temporal regulation of different biological processes. Recently, we unified these variations and argued that a steric clash between active site residues (corresponding to positions 12 and 61 of Ras) governs whether a GTPase utilizes the cis-Gln or the trans-Gln (from the GAP) for catalysis...
November 2, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29065764/recognition-and-stabilization-of-geranylgeranylated-human-rab5-by-the-gdp-dissociation-inhibitor-gdi
#6
Eileen Edler, Matthias Stein
The small GTPase Rab5 is the key regulator of early endosomal fusion. It is post-translationally modified by covalent attachment of two geranylgeranyl (GG) chains to adjacent cysteine residues of the C-terminal hypervariable region (HVR). The GDP dissociation inhibitor (GDI) recognizes membrane-associated Rab5(GDP) and serves to release it into the cytoplasm where it is kept in a soluble state. A detailed new structural and dynamic model for human Rab5(GDP) recognition and binding with human GDI at the early endosome membrane and in its dissociated state is presented...
October 25, 2017: Small GTPases
https://www.readbyqxmd.com/read/29058791/in-vitro-and-in-vivo-effect-of-pd-1-pd-l1-blockade-on-microglia-macrophage-activation-and-t-cell-subset-balance-in-cryptococcal-meningitis
#7
Yuan-Mei Che, Yi Zhang, Ming Li, Xiao-Peng Li, Lun-Li Zhang
This study aimed to investigate the PD-1/ PD-L1 signaling pathway and its effects the activation of microglia/macrophage and balancing T cell subsets in cryptococcal meningitis (CM). A total of 126 CM patients and 126 healthy individuals were recruited for the study. The CM patients were treated with amphotericin B (AmB). Seventy five C57BL/6 mice were grouped into the normal control, CM model, CM + AmB, sham and CM + PD-1 antibodies (Ab) groups. CD4(+) and CD8(+) T cells as well as microglia/macrophages were analyzed by means of flow cytometry...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29056935/the-atypical-receptor-ccrl2-c-c-chemokine-receptor-like-2-does-not-act-as-a-decoy-receptor-in-endothelial-cells
#8
Chiara Mazzotti, Vincenzo Gagliostro, Daniela Bosisio, Annalisa Del Prete, Laura Tiberio, Marcus Thelen, Silvano Sozzani
C-C chemokine receptor-like 2 (CCRL2) is a non-signaling seven-transmembrane domain (7-TMD) receptor related to the atypical chemokine receptor (ACKR) family. ACKRs bind chemokines but do not activate G protein-dependent signaling or cell functions. ACKRs were shown to regulate immune functions in vivo by their ability to scavenge chemokines from the local environment. This study was performed to investigate whether CCRL2 shares two of the main characteristics of ACKRs, namely the ability to internalize and scavenge the ligands...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29031718/g%C3%AE-s-regulates-glucagon-like-peptide-1-receptor-mediated-cyclic-amp-generation-at%C3%A2-rab5-endosomal-compartment
#9
Shravan Babu Girada, Ramya S Kuna, Shilpak Bele, Zhimeng Zhu, N R Chakravarthi, Richard D DiMarchi, Prasenjit Mitra
OBJECTIVE: Upon activation, G protein coupled receptors (GPCRs) associate with heterotrimeric G proteins at the plasma membrane to initiate second messenger signaling. Subsequently, the activated receptor experiences desensitization, internalization, and recycling back to the plasma membrane, or it undergoes lysosomal degradation. Recent reports highlight specific cases of persistent cyclic AMP generation by internalized GPCRs, although the functional significance and mechanistic details remain to be defined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28980867/nrbf2-is-involved-in-the-autophagic-degradation-process-of-app-ctfs-in-alzheimer-disease-models
#10
Chuanbin Yang, Cui-Zan Cai, Ju-Xian Song, Jie-Qiong Tan, Siva Sundara Kumar Durairajan, Ashok Iyaswamy, Ming-Yue Wu, Lei-Lei Chen, Zhenyu Yue, Min Li, Jia-Hong Lu
Alzheimer disease (AD) is the most common neurodegenerative disease characterized by the deposition of amyloid plaque in the brain. The autophagy-associated PIK3C3-containing phosphatidylinositol 3-kinase (PtdIns3K) complex has been shown to interfere with APP metabolism and amyloid beta peptide (Aβ) homeostasis via poorly understood mechanisms. Here we report that NRBF2 (nuclear receptor binding factor 2), a key component and regulator of the PtdIns3K, is involved in APP-CTFs homeostasis in AD cell models...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28979185/the-membrane-glycoprotein-m6a-endocytic-recycling-pathway-involves-clathrin-mediated-endocytosis-and-affects-neuronal-synapses
#11
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/28968219/site-specific-monoubiquitination-downregulates-rab5-by-disrupting-effector-binding-and-guanine-nucleotide-conversion
#12
Donghyuk Shin, Wooju Na, Ji-Hyung Lee, Gyuhee Kim, Jiseok Baek, Seok Hee Park, Cheol Yong Choi, Sangho Lee
Rab GTPases, which are involved in intracellular trafficking pathways, have recently been reported to be ubiquitinated. However, the functions of ubiquitinated Rab proteins remain unexplored. Here we show that Rab5 is monoubiquitinated on K116, K140, and K165. Upon co-transfection with ubiquitin, Rab5 exhibited abnormalities in endosomal localization and EGF-induced EGF receptor degradation. Rab5 K140R and K165R mutants restored these abnormalities, whereas K116R did not. We derived structural models of individual monoubiquitinated Rab5 proteins (mUbRab5s) by solution scattering and observed different conformational flexibilities in a site-specific manner...
October 2, 2017: ELife
https://www.readbyqxmd.com/read/28956766/porcine-hemagglutinating-encephalomyelitis-virus-enters-neuro-2a-cells-via-clathrin-mediated-endocytosis-in-a-rab5-cholesterol-and-ph-dependent-manner
#13
Zi Li, Kui Zhao, Yungang Lan, Xiaoling Lv, Shiyu Hu, Jiyu Guan, Huijun Lu, Jing Zhang, Junchao Shi, Yawen Yang, Deguang Song, Feng Gao, Wenqi He
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that invades the central nervous system (CNS) in piglets. Although important progress has been made toward understanding the biology of PHEV, many aspects of its life cycle remain obscure. Here we dissected the molecular mechanism underlying cellular entry and intracellular trafficking of PHEV in mouse neuroblastoma (Neuro-2a) cells. We first performed a thin-section transmission electron microscopy (TEM) assay to characterize the kinetics of PHEV, and we found that viral entry and transfer occur via membranous coating-mediated endo- and exocytosis...
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28934205/a-rab5-gtpase-module-is-important-for-autophagosome-closure
#14
Fan Zhou, Shenshen Zou, Yong Chen, Zhanna Lipatova, Dan Sun, Xiaolong Zhu, Rui Li, Zulin Wu, Weiming You, Xiaoxia Cong, Yiting Zhou, Zhiping Xie, Valeriya Gyurkovska, Yutao Liu, Qunli Li, Wenjing Li, Jie Cheng, Yongheng Liang, Nava Segev
In the conserved autophagy pathway, the double-membrane autophagosome (AP) engulfs cellular components to be delivered for degradation in the lysosome. While only sealed AP can productively fuse with the lysosome, the molecular mechanism of AP closure is currently unknown. Rab GTPases, which regulate all intracellular trafficking pathways in eukaryotes, also regulate autophagy. Rabs function in GTPase modules together with their activators and downstream effectors. In yeast, an autophagy-specific Ypt1 GTPase module, together with a set of autophagy-related proteins (Atgs) and a phosphatidylinositol-3-phosphate (PI3P) kinase, regulates AP formation...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28928467/cross-talk-between-mir-471-5p-and-autophagy-component-proteins-regulates-lc3-associated-phagocytosis-lap-of-apoptotic-germ-cells
#15
Subbarayalu Panneerdoss, Suryavathi Viswanadhapalli, Nourhan Abdelfattah, Benjamin C Onyeagucha, Santosh Timilsina, Tabrez A Mohammad, Yidong Chen, Michael Drake, Kristiina Vuori, T Rajendra Kumar, Manjeet K Rao
Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28918952/a-dual-function-for-prickle-in-regulating-frizzled-stability-during-feedback-dependent-amplification-of-planar-polarity
#16
Samantha J Warrington, Helen Strutt, Katherine H Fisher, David Strutt
The core planar polarity pathway coordinates epithelial cell polarity during animal development, and loss of its activity gives rise to a range of defects, from aberrant morphogenetic cell movements to failure to correctly orient structures, such as hairs and cilia. The core pathway functions via a mechanism involving segregation of its protein components to opposite cells ends, where they form asymmetric intracellular complexes that couple cell-cell polarity. This segregation is a self-organizing process driven by feedback interactions between the core proteins themselves...
September 25, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28899395/role-of-rab5-in-the-formation-of-macrophage-derived-foam-cell
#17
Lokwern Chan, Jin Hong, Junjie Pan, Jian Li, Zhichao Wen, Haiming Shi, Jianping Ding, Xinping Luo
BACKGROUND: Foam cells play a key role in the occurrence and pathogenesis of atherosclerosis. Its formation starts with the ingestion of oxidized low-density lipoprotein (oxLDL). The process is associated with Ras related protein in brain 5 (Rab5) which plays a critical role in regulating endocytosis and early endosomal trafficking. Base on this, we presumed that Rab5 might participate in the maturation of foam cell. The aim of this study is to investigate the effect of Rab5 on macrophage cholesterol during the evolvement of macrophage when induced by oxLDL to the formation of foam cell...
September 12, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28878211/assay-to-visualize-specific-protein-oxidation-reveals-spatio-temporal-regulation-of-shp2
#18
Ryouhei Tsutsumi, Jana Harizanova, Rabea Stockert, Katrin Schröder, Philippe I H Bastiaens, Benjamin G Neel
Reactive oxygen species are produced transiently in response to cell stimuli, and function as second messengers that oxidize target proteins. Protein-tyrosine phosphatases are important reactive oxygen species targets, whose oxidation results in rapid, reversible, catalytic inactivation. Despite increasing evidence for the importance of protein-tyrosine phosphatase oxidation in signal transduction, the cell biological details of reactive oxygen species-catalyzed protein-tyrosine phosphatase inactivation have remained largely unclear, due to our inability to visualize protein-tyrosine phosphatase oxidation in cells...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28874679/the-endosomal-neuronal-proteins-nsg1-neep21-and-nsg2-p19-are-itinerant-not-resident-proteins-of-dendritic-endosomes
#19
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
https://www.readbyqxmd.com/read/28872124/in-vitro-polymerization-of-f-actin-on-early-endosomes
#20
Olivia Muriel, Cameron Christopher Scott, Jorge Larios, Vicent Mercier, Jean Gruenberg
Many early endosome functions, particularly cargo protein sorting and membrane deformation, depend on patches of short F-actin filaments nucleated onto the endosomal membrane. We have established a microscopy-based in vitro assay that reconstitutes the nucleation and polymerization of F-actin on early endosomal membranes in test tubes, thus rendering this complex series of reactions amenable to genetic and biochemical manipulations. Endosomal fractions are prepared by floatation in sucrose gradients from cells expressing the early endosomal protein GFP-RAB5...
August 28, 2017: Journal of Visualized Experiments: JoVE
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