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https://www.readbyqxmd.com/read/28504462/endocytic-activity-of-hiv-1-vpu-phosphoserine-dependent-interactions-with-clathrin-adaptors
#1
Charlotte A Stoneham, Rajendra Singh, Xiaofei Jia, Yong Xiong, John Guatelli
HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune-evasion, triggering ubiquitin-mediated degradation of some targets but also modulating endosomal trafficking to deplete them from the plasma membrane. Interactions between Vpu and the heterotetrameric clathrin adaptors AP-1 and AP-2 have been described, yet the molecular basis and functional roles of such interactions are incompletely defined. To investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8 α-chain...
May 14, 2017: Traffic
https://www.readbyqxmd.com/read/28485883/cell-survival-and-protein-secretion-associated-with-golgi-integrity-in-response-to-golgi-stress-inducing-agents
#2
Tatiana I Ignashkova, Mathieu Gendarme, Katrin Peschk, Hans-Michael Eggenweiler, Ralph K Lindemann, Jan H Reiling
The Golgi apparatus is part of the secretory pathway and of central importance for modification, transport and sorting of proteins and lipids. ADP-ribosylation factors, whose activation can be blocked by brefeldin A, play a major role in functioning of the Golgi network and regulation of membrane traffic and are also involved in proliferation and migration of cancer cells. Due to high cytotoxicity and poor bioavailability brefeldin A has not passed the pre-clinical stage of drug development. Recently, AMF-26 and golgicide A have been described as novel inhibitors of the Golgi system with anti-tumor or bactericidal properties...
May 9, 2017: Traffic
https://www.readbyqxmd.com/read/28485852/vaccinia-virus-proteins-a36-and-f12-e2-show-strong-preferences-for-different-klc-isoforms
#3
William N D Gao, David C J Carpentier, Helen A Ewles, Stacey-Ann Lee, Geoffrey L Smith
Vaccinia virus (VACV) utilises microtubule-mediated trafficking at several stages of its life cycle, of which virus egress is the most intensely studied. During egress VACV proteins A36, F12 and E2 are involved in kinesin-1 interactions, however the roles of these proteins remain poorly understood. A36 forms a direct link between virions and kinesin-1, yet in its absence VACV egress still occurs on microtubules. During a co-immunoprecipitation screen to seek an alternative link between virions and kinesin, A36 was found to bind isoform KLC1 rather than KLC2...
May 9, 2017: Traffic
https://www.readbyqxmd.com/read/28477369/snx27-interactome-in-t-lymphocytes-identifies-zo-2-dynamic-redistribution-at-the-immune-synapse
#4
María Tello-Lafoz, Gonzalo Martínez-Martínez, Cristina Rodríguez-Rodríguez, Juan Pablo Albar, Morgan Huse, Severine Gharbi, Isabel Merida
T lymphocyte recognition of antigens leads to the formation of a highly organized structure termed immune synapse (IS) by analogy with the nervous synapse. Sorting nexin 27 (SNX27) controls the endosomal traffic of PDZ domain-interacting proteins, and its alteration is associated with impaired synaptic function and neurological diseases. In T lymphocytes SNX27-positive vesicles polarize to the IS, the identity of SNX27 interactors in these conditions nonetheless remains unknown. Here we used proteomics to analyze the SNX27 interactome purified from IS-forming T cells, and confirmed the conserved nature of the SNX27/WASH/retromer association in hematopoietic cells...
May 6, 2017: Traffic
https://www.readbyqxmd.com/read/28471062/pharmacologically-increasing-microtubule-acetylation-corrects-stress-exacerbated-effects-of-organophosphates-on-neurons
#5
Anand N Rao, Ankita Patil, Zachary D Brodnik, Liang Qiang, Rodrigo A España, Kimberly A Sullivan, Mark M Black, Peter W Baas
Many veterans of the 1990-1991 Gulf War contracted Gulf War Illness (GWI), a multisymptom disease that primarily affects the nervous system. Here, we treated cultures of human or rat neurons with diisopropyl fluorophosphate (DFP), an analog of sarin, one of the organophosphate (OP) toxicants to which the military veterans were exposed. All observed cellular defects produced by DFP were exacerbated by pretreatment with corticosterone or cortisol, which, in rat and human neurons, respectively, serves in our experiments to mimic the physical stress endured by soldiers during the war...
May 4, 2017: Traffic
https://www.readbyqxmd.com/read/28471037/oxysterol-binding-protein-recruitment-and-activity-at-the-er-golgi-interface-are-independent-of-sac1
#6
Mark Charman, Asako Goto, Neale D Ridgway
Oxysterol binding protein (OSBP) localizes to endoplasmic reticulum (ER)-Golgi contact sites where it transports cholesterol and phosphatidylinositol 4-phosphate (PI-4P), and activates lipid transport and biosynthetic activities. The PI-4P phosphatase Sac1 cycles between the ER and Golgi apparatus where it potentially regulates OSBP activity. Here we examined whether the ER-Golgi distribution of endogenous or ectopically- expressed Sac1 influences OSBP activity. OSBP and Sac1 co-localized at apparent ER-Golgi contact sites in response to 25-hydroxycholesterol (25OH), cholesterol-depletion and p38 MAPK inhibitors...
May 4, 2017: Traffic
https://www.readbyqxmd.com/read/28471021/syntaxin-4-mediates-endosome-recycling-for-lytic-granule-exocytosis-in-cytotoxic-t-lymphocytes
#7
Waldo A Spessott, Maria L Sanmillan, Vineet V Kulkarni, Margaret E McCormick, Claudio G Giraudo
Adaptive and innate immunity utilize the perforin-killing pathway to eliminate virus-infected or cancer cells. Cytotoxic T-lymphocytes (CTLs) and Natural Killer cells mediate this process by releasing toxic proteins at the contact area with target cells known as immunological synapse (IS). Formation of a stable IS and exocytosis of toxic proteins requires persistent fusion of Rab11a recycling endosomes with the plasma membrane (PM) that may assure the delivery of key effector proteins. Despite the importance of the recycling endosomal compartment, the membrane fusion proteins that control this process at the IS remain elusive...
May 4, 2017: Traffic
https://www.readbyqxmd.com/read/28421662/the-outer-membrane-vesicles-secretion-system-type-zero
#8
REVIEW
Andrea Guerrero-Mandujano, Cecilia Hernández-Cortez, Jose Antonio Ibarra, Graciela Castro-Escarpulli
Gram-negative bacteria have mechanisms through which they can colonize and survive in different environments, such as the secretion systems types (1-6) that have been widely studied and characterized. Nowadays, some authors have proposed extracellular structures, such as the outer membrane vesicles (OMVs), to be considered as an additional and independent secretion system. The OMVs are spherical particles of 50-250 nm in diameter; they originate in the outer membrane, and therefore they have a very similar composition to the latter...
April 19, 2017: Traffic
https://www.readbyqxmd.com/read/28407399/abnormal-rab11-rab8-vesicles-cluster-in-enterocytes-of-patients-with-microvillus-inclusion-disease
#9
Georg F Vogel, Andreas R Janecke, Iris M Krainer, Karin Gutleben, Barbara Witting, Sally G Mitton, Sahar Mansour, Antje Ballauff, Joseph T Roland, Amy C Engevik, Ernest Cutz, Thomas Müller, James R Goldenring, Lukas A Huber, Michael W Hess
Microvillus Inclusion Disease (MVID) is a congenital enteropathy characterized by accumulation of vesiculo-tubular endomembranes in the subapical cytoplasm of enterocytes, historically termed "secretory granules". However, neither their identity nor pathophysiological significance is well defined. Using immunoelectron microscopy and tomography we studied biopsies from MVID patients (3x Myosin 5b mutations, 1x Syntaxin3 mutation) and compared them to controls and genome-edited CaCo2 cell models, harboring relevant mutations...
April 13, 2017: Traffic
https://www.readbyqxmd.com/read/28393448/spatial-specific-functions-in-retrograde-neuronal-signalling
#10
REVIEW
Eitan Erez Zahavi, Roy Maimon, Eran Perlson
Neurons are highly polarized cells, possessing long axons that can extend to more than 1-m long in adult humans. In order to survive and maintain proper functions, neurons have to respond accurately in both space and time to intracellular or intercellular cues. The regulation of these comprehensive responses involves ligand-receptor interactions, trafficking and local protein synthesis. Alterations in these mechanisms can lead to cellular dysfunction and disease. Although studies on the transport and localization of signalling endosomes along the axon have shed light on some central pathways of neuronal survival and growth as well as synapse function, little is known about the spatiotemporal mechanisms that allow the same molecule to signal differently at diverse subcellular locations and in specific neuronal populations...
April 10, 2017: Traffic
https://www.readbyqxmd.com/read/28382714/enzyme-reversal-to-explore-the-function-of-yeast-e3-ubiquitin-ligases
#11
Chris MacDonald, Stanley Winistorfer, R Marshall Pope, Michael E Wright, Robert C Piper
The covalent attachment of ubiquitin onto proteins can elicit a variety of downstream consequences. Attachment is mediated by a large array of E3 ubiquitin ligases, each thought be subject to regulatory control and to have a specific repertoire of substrates. Assessing the biological roles of ligases, and in particular, identifying their biologically relevant substrates has been a persistent yet challenging question. In this study we describe tools that may help achieve both of these goals. We describe a strategy whereby the activity of a ubiquitin ligase has been enzymatically reversed, accomplished by fusing it to a catalytic domain of an exogenous deubiquitinating enzyme...
April 6, 2017: Traffic
https://www.readbyqxmd.com/read/28371052/recent-progress-in-autophagic-lysosome-reformation
#12
REVIEW
Yang Chen, Li Yu
Autophagic lysosome reformation (ALR) is the terminal step of autophagy and is essential for maintaining lysosome homeostasis during autophagy. During ALR, tubules are extruded from autolysosomes, and small vesicles named proto-lysosomes, which are composed of lysosomal membrane components, are generated from these tubules. Eventually, proto-lysosomes mature into functional lysosomes. In this review, we will summarize recent progress in understanding the regulation, mechanisms and physiological functions of ALR...
March 31, 2017: Traffic
https://www.readbyqxmd.com/read/28371106/cell-biology-in-china-focusing-on-the-lysosome
#13
REVIEW
Chonglin Yang, Xiaochen Wang
The view that lysosomes are merely the recycling bins of the cell has changed greatly during recent years. Lysosomes are now known to play a central role in signal transduction, cellular adaptation, plasma membrane repair, immune responses and many other fundamental cellular processes. In conjunction with the seminal discoveries made by international colleagues, many important questions regarding lysosomes are being addressed by Chinese scientists. In this review, we briefly summarize recent exciting findings in China on lysosomal signaling, biogenesis, integrity and physiological functions...
March 30, 2017: Traffic
https://www.readbyqxmd.com/read/28371047/hai-2-stabilizes-inhibits-and-regulates-sea-cleavage-dependent-secretory-transport-of-matriptase
#14
Annika W Nonboe, Oliver Krigslund, Christoffer Soendergaard, Signe Skovbjerg, Stine Friis, Martin N Andersen, Vincent Ellis, Makiko Kawaguchi, Hiroaki Kataoka, Thomas H Bugge, Lotte K Vogel
It has recently been shown that hepatocyte growth factor activator inhibitor-2 (HAI-2) is able to suppress carcinogenesis induced by overexpression of matriptase, as well as cause regression of individual established tumors in a mouse model system. However, the role of HAI-2 is poorly understood. In this study, we describe 3 mutations in the binding loop of the HAI-2 Kunitz domain 1 (K42N, C47F and R48L) that cause a delay in the SEA domain cleavage of matriptase, leading to accumulation of non-SEA domain cleaved matriptase in the endoplasmic reticulum (ER)...
March 28, 2017: Traffic
https://www.readbyqxmd.com/read/28321960/hiv-infection-is-influenced-by-dynamin-at-3-independent-points-in-the-viral-life-cycle
#15
Anupriya Aggarwal, Tina L Hitchen, Lars Ootes, Samantha McAllery, Andrew Wong, Khanh Nguyen, Adam McCluskey, Phillip J Robinson, Stuart G Turville
CD4 T cells are important cellular targets for HIV-1, yet the primary site of HIV fusion remains unresolved. Candidate fusion sites are either the plasma membrane or from within endosomes. One area of investigation compounding the controversy of this field, is the role of the protein dynamin in the HIV life cycle. To understand the role of dynamin in primary CD4 T cells we combined dynamin inhibition with a series of complementary assays based on single particle tracking, HIV fusion, detection of HIV DNA products and active viral transcription...
March 21, 2017: Traffic
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
#16
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 the 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
#17
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/28248450/regulation-of-dynein-dynactin-driven-vesicular-transport
#18
REVIEW
Jia-Jia Liu
Most of the long-range intracellular movements of vesicles, organelles and other cargoes are driven by microtubule (MT)-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 MTs. In this article, I 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 MT tracks...
March 1, 2017: Traffic
https://www.readbyqxmd.com/read/28513089/editorial-overview-celebrating-the-advances-in-cell-biology-from-china
#19
EDITORIAL
Sharon A Tooze, Quan Chen
No abstract text is available yet for this article.
June 2017: Traffic
https://www.readbyqxmd.com/read/28267259/the-axonal-transport-motor-kinesin-2-navigates-microtubule-obstacles-via-protofilament-switching
#20
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...
May 2017: Traffic
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