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https://www.readbyqxmd.com/read/28295920/importin-%C3%AE-1-targeting-by-hepatitis-c-virus-ns3-4a-protein-restricts-irf3-and-nf-%C3%AE%C2%BAb-signaling-of-ifnb1-antiviral-response
#1
Bridget Gagné, Nicolas Tremblay, Alex Y Park, Martin Baril, Daniel Lamarre
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection...
March 13, 2017: Traffic
https://www.readbyqxmd.com/read/28276191/deleting-the-dag-kinase-dgk1-augments-yeast-vacuole-fusion-through-increased-ypt7-activity-and-altered-membrane-fluidity
#2
Gregory E Miner, Matthew L Starr, Logan R Hurst, Rutilio A Fratti
Diacylglycerol (DAG) is a fusogenic lipid that can be produced through phospholipase C activity on phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ], or through phosphatidic acid (PA) phosphatase activity. The fusion of Saccharomyces cerevisiae vacuoles requires DAG, PA and PI(4,5)P2 , and the production of these lipids is thought to provide temporally specific stoichiometries that are critical for each stage of fusion. Furthermore, DAG and PA can be interconverted by the DAG kinase Dgk1 and the PA phosphatase Pah1...
March 9, 2017: Traffic
https://www.readbyqxmd.com/read/28267259/the-axonal-transport-motor-kinesin-2-navigates-microtubule-obstacles-via-protofilament-switching
#3
Gregory J Hoeprich, Keith J Mickolajczyk, Shane R Nelson, William O Hancock, Christopher L Berger
Axonal transport involves kinesin motors trafficking cargo along microtubules that are rich in microtubule-associated proteins (MAPs). Much attention has focused on the behavior of kinesin-1 in the presence of MAPs, which has overshadowed understanding the contribution of other kinesins such as kinesin-2 in axonal transport. We have previously shown that, unlike kinesin-1, kinesin-2 in vitro motility is insensitive to the neuronal MAP Tau. However, the mechanism by which kinesin-2 efficiently navigates Tau on the microtubule surface is unknown...
March 7, 2017: Traffic
https://www.readbyqxmd.com/read/28266105/c9orf72-at-the-intersection-of-lysosome-cell-biology-and-neurodegenerative-disease
#4
REVIEW
Joseph Amick, Shawn M Ferguson
The discovery that expansion of a hexanucleotide repeat within a non-coding region of the C9orf72 gene causes amyotrophic lateral sclerosis and frontotemporal dementia raised questions about C9orf72 protein function and potential disease relevance. The major predicted structural feature of the C9orf72 protein is a DENN domain. As DENN domains are best characterized for regulation of specific Rab GTPases, it has been proposed that C9orf72 may also act through regulation of a GTPase target. Recent genetic and cell biological studies furthermore indicate that the C9orf72 protein functions at lysosomes as part of a larger complex that also contains the Smith-Magenis Chromosome Region 8 (SMCR8) and WD repeat-containing protein 41 (WDR41) proteins...
March 7, 2017: Traffic
https://www.readbyqxmd.com/read/28248450/regulation-of-dynein-dynactin-driven-vesicular-transport
#5
REVIEW
Jia-Jia Liu
Most of the long-range intracellular movements of vesicles, organelles and other cargoes are driven by microtubule-based molecular motors. Cytoplasmic dynein, a multisubunit protein complex, with the aid of dynactin, drives transport of a wide variety of cargoes towards the minus end of microtubules. In the present article, we review our current understanding of the mechanisms underlying spatiotemporal regulation of dynein-dynactin-driven vesicular transport with a special emphasis on the many steps of directional movement along microtubule tracks...
March 1, 2017: Traffic
https://www.readbyqxmd.com/read/28248449/protein-transport-in-growing-and-steady-state-cilia
#6
REVIEW
Karl F Lechtreck, Julie C Van De Weghe, J Aaron Harris, Peiwei Liu
Cilia and eukaryotic flagella are threadlike cell extensions with motile and sensory functions. Their assembly requires intraflagellar transport (IFT), a bidirectional motor-driven transport of protein carriers along the axonemal microtubules. IFT moves ample amounts of structural proteins including tubulin into growing cilia likely explaining its critical role for assembly. IFT continues in non-growing cilia contributing to a variety of processes ranging from axonemal maintenance and the export of non-ciliary proteins to cell locomotion and ciliary signaling...
March 1, 2017: Traffic
https://www.readbyqxmd.com/read/28224728/%C3%AE-2-dependent-endocytosis-of-n-cadherin-is-regulated-by-%C3%AE-catenin-to-facilitate-neurite-outgrowth
#7
Yi-Ting Chen, Chin-Yin Tai
Circuit formation in the brain requires neurite outgrowth throughout development to establish synaptic contacts with target cells. Active endocytosis of several adhesion molecules facilitates the dynamic exchange of these molecules at the surface and promotes neurite outgrowth in developing neurons. The endocytosis of N-cadherin, a calcium-dependent adhesion molecule, has been implicated in the regulation of neurite outgrowth, but the mechanism remains unclear. Here, we identified that a fraction of N-cadherin internalizes through clathrin-mediated endocytosis (CME)...
February 22, 2017: Traffic
https://www.readbyqxmd.com/read/28220989/global-and-local-mechanisms-sustain-axonal-proteostasis-of-transmembrane-proteins
#8
REVIEW
Víctor Hugo Cornejo, Alejandro Luarte, Andrés Couve
The control of neuronal protein homeostasis or proteostasis is tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size...
February 21, 2017: Traffic
https://www.readbyqxmd.com/read/28191915/routes-and-mechanisms-of-post-endosomal-cholesterol-trafficking-a-story-that-never-ends
#9
REVIEW
Jie Luo, Luyi Jiang, Hongyuan Yang, Bao-Liang Song
Mammalian cells acquire most exogenous cholesterol through receptor-mediated endocytosis of low-density lipoproteins (LDLs). After internalization, LDL cholesteryl esters are hydrolyzed to release free cholesterol, which then translocates to late endosomes (LEs)/lysosomes (LYs) and incorporates into the membranes by coordinated actions of Niemann-Pick type C (NPC) 1 and NPC2 proteins. However, how cholesterol exits LEs/LYs and moves to other organelles remain largely unclear. Growing evidence has suggested that nonvesicular transport is critically involved in the post-endosomal cholesterol trafficking...
February 13, 2017: Traffic
https://www.readbyqxmd.com/read/28156030/er-to-golgi-blockade-of-nascent-desmosomal-cadherins-in-serca2-inhibited-keratinocytes-implications-for-darier-s-disease
#10
Ning Li, Moonhee Park, Shengxiang Xiao, Zhi Liu, Luis A Diaz
Darier's disease (DD) is an autosomal dominantly inherited skin disorder caused by mutations in SERCA2, a Ca(2+) pump that transports Ca(2+) from the cytosol to the endoplasmic reticulum (ER). Loss of desmosomes and keratinocyte cohesion is a characteristic feature of DD. Desmosomal cadherins (DC) are Ca(2+) -dependent transmembrane adhesion proteins of desmosomes, which are mislocalized in the lesional but not perilesional skin of DD. We show here that inhibition of SERCA2 by two distinct inhibitors results in accumulation of DC precursors in keratinocytes, indicating ER-to-Golgi transport of nascent DC is blocked...
February 3, 2017: Traffic
https://www.readbyqxmd.com/read/28128492/beyond-attachment-roles-of-dc-sign-in-dengue-virus-infection
#11
Ping Liu, Marc Ridilla, Pratik Patel, Laurie Betts, Emily Gallichotte, Lidea Shahidi, Nancy L Thompson, Ken Jacobson
DC-SIGN, a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS, and dengue. A controversial question has been whether DC-SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand-off to another receptor or a co-receptor for internalization. To examine this question, we used four cell types: human immature dendritic cells and NIH3T3 cells expressing either wild type DC-SIGN or two internalization-deficient DC-SIGN mutants, in which either the three cytoplasmic internalization motifs are silenced by alanine substitutions or the cytoplasmic region is truncated...
January 27, 2017: Traffic
https://www.readbyqxmd.com/read/28019081/dna-based-probes-for-flow-cytometry-analysis-of-endocytosis-and-recycling
#12
Claire Dumont, Ewa Czuba, Moore Chen, Jose A Villadangos, Angus P R Johnston, Justine D Mintern
The internalization of proteins plays a key role in cell development, cell signaling and immunity. We have previously developed a specific hybridization internalization probe (SHIP) to quantitate the internalization of proteins and particles into cells. Herein, we extend the utility of SHIP to examine both the endocytosis and recycling of surface receptors using flow cytometry. SHIP was used to monitor endocytosis of membrane-bound transferrin receptor and its soluble ligand transferrin. SHIP enabled measurements of the proportion of surface molecules internalized, the internalization kinetics and the proportion and rate of internalized molecules that recycle to the cell surface with time...
December 26, 2016: Traffic
https://www.readbyqxmd.com/read/28067430/exogenous-lysophospholipids-with-large-head-groups-perturb-clathrin-mediated-endocytosis
#13
Ieva Ailte, Anne Berit D Lingelem, Audun S Kvalvaag, Simona Kavaliauskiene, Andreas Brech, Gerbrand Koster, Paul G Dommersnes, Jonas Bergan, Tore Skotland, Kirsten Sandvig
In this study, we have investigated how clathrin-dependent endocytosis is affected by exogenously added lysophospholipids (LPLs). Addition of LPLs with large head groups strongly inhibits transferrin (Tf) endocytosis in various cell lines, while LPLs with small head groups do not. Electron and total internal reflection fluorescence microscopy (EM and TIRF) reveal that treatment with lysophosphatidylinositol (LPI) with the fatty acyl group C18:0 leads to reduced numbers of invaginated clathrin-coated pits (CCPs) at the plasma membrane, fewer endocytic events per membrane area and increased lifetime of CCPs...
March 2017: Traffic
https://www.readbyqxmd.com/read/28035714/green-fluorescent-protein-tagged-apolipoprotein-e-a-useful-marker-for-the-study-of-hepatic-lipoprotein-egress
#14
Constantin N Takacs, Ursula Andreo, Rachel L Belote, Joan Pulupa, Margaret A Scull, Caroline E Gleason, Charles M Rice, Sanford M Simon
Apolipoprotein E (ApoE), a component of very-low-density and high-density lipoproteins, participates in many aspects of lipid transport in the bloodstream. Underscoring its important functions, ApoE isoforms have been associated with metabolic and circulatory disease. ApoE is also incorporated into hepatitis C virus (HCV) particles, and promotes their production and infectivity. Live cell imaging analysis of ApoE behavior during secretion from producing cells thus has the potential to reveal important details regarding lipoprotein and HCV particle biogenesis and secretion from cells...
March 2017: Traffic
https://www.readbyqxmd.com/read/28000370/amyloid-precursor-protein-traffics-from-the-golgi-directly-to-early-endosomes-in-an-arl5b-and-ap4-dependent-pathway
#15
Wei Hong Toh, Jing Zhi A Tan, Khalisah L Zulkefli, Fiona J Houghton, Paul A Gleeson
The intracellular trafficking and proteolytic processing of the membrane-bound amyloid precursor protein (APP) are coordinated events leading to the generation of pathogenic amyloid-beta (Aβ) peptides. The membrane transport of newly synthesized APP from the Golgi to the endolysosomal system is not well defined, yet it is likely to be critical for regulating its processing by β-secretase (BACE1) and γ-secretase. Here, we show that the majority of newly synthesized APP is transported from the trans-Golgi network (TGN) directly to early endosomes and then subsequently to the late endosomes/lysosomes with very little transported to the cell surface...
March 2017: Traffic
https://www.readbyqxmd.com/read/27991712/targeting-of-tail-anchored-membrane-proteins-to-subcellular-organelles-in-toxoplasma-gondii
#16
Leah R Padgett, Gustavo Arrizabalaga, William J Sullivan
Proper protein localization is essential for critical cellular processes, including vesicle-mediated transport and protein translocation. Tail-anchored (TA) proteins are integrated into organellar membranes via the C-terminus, orienting the N-terminus towards the cytosol. Localization of TA proteins occurs posttranslationally and is governed by the C-terminus, which contains the integral transmembrane domain (TMD) and targeting sequence. Targeting of TA proteins is dependent on the hydrophobicity of the TMD as well as the length and composition of flanking amino acid sequences...
March 2017: Traffic
https://www.readbyqxmd.com/read/28097732/fundamental-mechanisms-deliver-the-nobel-prize-to-ohsumi
#17
Sharon A Tooze, Lisa A Hannan, Michael S Marks, Tom H Stevens, Trina A Schroer
No abstract text is available yet for this article.
February 2017: Traffic
https://www.readbyqxmd.com/read/28026081/distinct-complexes-of-yeast-snx4-family-snx-bars-mediate-retrograde-trafficking-of-snc1-and-atg27
#18
Mengxiao Ma, Christopher G Burd, Richard J Chi
The yeast SNX4 sub-family of sorting nexin containing a Bin-Amphiphysin-Rvs domain (SNX-BAR) proteins, Snx4/Atg24, Snx41 and Atg20/Snx42, are required for endocytic recycling and selective autophagy. Here, we show that Snx4 forms 2 functionally distinct heterodimers: Snx4-Atg20 and Snx4-Snx41. Each heterodimer coats an endosome-derived tubule that mediates retrograde sorting of distinct cargo; the v-SNARE, Snc1, is a cargo of the Snx4-Atg20 pathway, and Snx4-Snx41 mediates retrograde sorting of Atg27, an integral membrane protein implicated in selective autophagy...
February 2017: Traffic
https://www.readbyqxmd.com/read/27976831/the-c-terminal-tails-of-heterotrimeric-kinesin-2-motor-subunits-directly-bind-to-%C3%AE-tubulin1-possible-implications-for-cilia-specific-tubulin-entry
#19
Mukul Girotra, Shalini Srivastava, Anuttama Kulkarni, Ayan Barbora, Kratika Bobra, Debnath Ghosal, Pavithra Devan, Amol Aher, Akanksha Jain, Dulal Panda, Krishanu Ray
The assembly of microtubule-based cytoskeleton propels the cilia and flagella growth. Previous studies have indicated that the kinesin-2 family motors transport tubulin into the cilia through intraflagellar transport. Here, we report a direct interaction between the C-terminal tail fragments of heterotrimeric kinesin-2 and α-tubulin1 isoforms in vitro. Blot overlay screen, affinity purification from tissue extracts, cosedimentation with subtilisin-treated microtubule and LC-ESI-MS/MS characterization of the tail-fragment-associated tubulin identified an association between the tail domains and α-tubulin1A/D isotype...
February 2017: Traffic
https://www.readbyqxmd.com/read/27976830/mitochondrial-protein-import-in-trypanosomes-expect-the-unexpected
#20
REVIEW
Anke Harsman, André Schneider
Mitochondria have many different functions, the most important one of which is oxidative phosphorylation. They originated from an endosymbiotic event between a bacterium and an archaeal host cell. It was the evolution of a protein import system that marked the boundary between the endosymbiotic ancestor of the mitochondrion and a true organelle that is under the control of the nucleus. In present day mitochondria more than 95% of all proteins are imported from the cytosol in a proces mediated by hetero-oligomeric protein complexes in the outer and inner mitochondrial membranes...
February 2017: Traffic
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