Editorial overview: Celebrating the advances in cell biology from China
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Source: Traffic - May 16, 2017 Category: Research Authors: Sharon A. Tooze, Quan Chen Tags: EDITORIAL Source Type: research
Issue Information
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Source: Traffic - May 16, 2017 Category: Research Tags: ISSUE INFORMATION Source Type: research
Pharmacologically increasing microtubule acetylation corrects stress ‐exacerbated effects of organophosphates on neurons
Abstract
Many veterans of the 1990–1991 Gulf War contracted Gulf War Illness, a multi‐symptom disease that primarily affects the nervous system. Here we treated cultures of human or rat neurons with diisopropylfluorophosphate (DFP), an analog of sarin, one of the organophosphate 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 the rat and human neurons respectively, serves in our experiments to mimic the physical stress endured by soldiers during the war. To best mimic the disease, DFP was use...
Source: Traffic - May 4, 2017 Category: Research Authors: Anand N. Rao, Ankita Patil, Zachary D. Brodnik, Liang Qiang, Rodrigo A. Espana, Kimberly A. Sullivan, Mark M. Black, Peter W. Baas Tags: ORIGINAL ARTICLE Source Type: research
Syntaxin 4 mediates endosome recycling for lytic granule exocytosis in cytotoxic T ‐lymphocytes
ABSTRACT
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...
Source: Traffic - May 4, 2017 Category: Research Authors: Waldo A. Spessott, Maria L. Sanmillan, Vineet V. Kulkarni, Margaret E. McCormick, Claudio G. Giraudo Tags: ORIGINAL ARTICLE Source Type: research
HAI ‐2 stabilizes, inhibits and regulates SEA‐cleavage‐dependent secretory transport of matriptase
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). We suggest that, like other known SEA domains, the matriptase SEA domain auto‐cleaves and reflects that correct oligomerization, maturation, and/or folding has been obtained. Our results suggest that the HAI‐2 Kunitz domain 1 mutants influence the flux of matriptase to the plasma membrane by affecting the oligomerization, maturation and/or folding of ma...
Source: Traffic - May 2, 2017 Category: Research Authors: 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 Tags: ORIGINAL ARTICLE Source Type: research
Endocytic Activity of HIV ‐1 Vpu: Phosphoserine‐dependent Interactions with Clathrin Adaptors
ABSTRACT
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‐ch...
Source: Traffic - May 1, 2017 Category: Research Authors: Charlotte A. Stoneham, Rajendra Singh, Xiaofei Jia, Yong Xiong, John Guatelli Tags: ORIGINAL ARTICLE Source Type: research
Vaccinia Virus Proteins A36 and F12/E2 Show Strong Preferences for Different KLC Isoforms
Abstract
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. The F12/E2 complex associates preferentially wit...
Source: Traffic - May 1, 2017 Category: Research Authors: William N. D. Gao, David C. J. Carpentier, Helen A. Ewles, Stacey ‐Ann Lee, Geoffrey L. Smith Tags: ORIGINAL ARTICLE Source Type: research
Cell survival and protein secretion associated with Golgi integrity in response to Golgi stress ‐inducing agents
Abstract
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 bact...
Source: Traffic - May 1, 2017 Category: Research Authors: Tatiana I. Ignashkova, Mathieu Gendarme, Katrin Peschk, Hans ‐Michael Eggenweiler, Ralph K. Lindemann, Jan H. Reiling Tags: ORIGINAL ARTICLE Source Type: research
SNX27 interactome in T lymphocytes identifies ZO ‐2 dynamic redistribution at the immune synapse
This study broadens our knowledge of SNX27 function in T lymphocytes, and suggests that pathways that delimit polarized structures in nervous and epithelial systems also participate in IS regulation.
Graphical abstract
The role of sorting nexin 27 (SNX27) in the recycling of PDZ‐interacting neuronal proteins has been widely studied. In T lymphocytes, SNX27 localizes to the immune synapse (IS) where its function remains poorly understood. Using a proteomic strategy, we identified SNX27 PDZ‐dependent and independent interactome in IS‐forming T cells. We showed that SNX27 participates in the dynamics of zona occluden...
Source: Traffic - May 1, 2017 Category: Research Authors: Mar ía Tello‐Lafoz, Gonzalo Martínez‐Martínez, Cristina Rodríguez‐Rodríguez, Juan Pablo Albar, Morgan Huse, Severine Gharbi, Isabel Merida Tags: ORIGINAL ARTICLE Source Type: research
Oxysterol binding protein recruitment and activity at the ER ‐Golgi interface are independent of Sac1
ABSTRACT
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 p...
Source: Traffic - May 1, 2017 Category: Research Authors: Mark Charman, Asako Goto, Neale D. Ridgway Tags: ORIGINAL ARTICLE Source Type: research
The Outer Membrane Vesicles: Secretion System Type zero
Abstract
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, to be considered as an additional and independent secretion system. The outer membrane vesicles are spherical particles of 50–250 nm in diameter; they originate in the outer membrane, therefore, they have a very similar composition to the latter. These particles can transport an important variety of biomolecule...
Source: Traffic - April 19, 2017 Category: Research Authors: Andrea Guerrero ‐Mandujano, Cecilia Hernández‐Cortez, J. Antonio Ibarra, Graciela Castro‐Escarpulli Tags: REVIEW Source Type: research
Abnormal Rab11 ‐Rab8‐vesicles cluster in enterocytes of patients with Microvillus Inclusion Disease
Abstract
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. Duodenal biopsies from two patients with novel Myosin 5b mutations and typical clin...
Source: Traffic - April 13, 2017 Category: Research Authors: 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 M üller, James R. Goldenring, Lukas A. Huber, Michael W. Hess Tags: CASE REPORT Source Type: research
Issue Information
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Source: Traffic - April 12, 2017 Category: Research Tags: ISSUE INFORMATION Source Type: research
HIV infection is influenced by dynamin at 3 independent points in the viral life cycle
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. We identify 3 levels of dynamin influence on the HIV life cycle. Firstly, dyn...
Source: Traffic - April 11, 2017 Category: Research Authors: Anupriya Aggarwal, Tina L. Hitchen, Lars Ootes, Samantha McAllery, Andrew Wong, Khanh Nguyen, Adam McCluskey, Phillip J. Robinson, Stuart G. Turville Tags: ORIGINAL ARTICLE Source Type: research
Enzyme reversal to explore the function of yeast E3 ubiquitin ‐ligases
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. We present a library of 72 ‘anti‐ligases’ that appear to work in a dominant‐negative fashion to stabilize their cognate substrates against ubiquitin‐dependent proteasomal and lysosomal degradation. We then used the ligase‐DUb library to screen for E3 ligases involved in post‐Golgi / endosomal trafficking. We identify ligases previously implicated in t...
Source: Traffic - April 6, 2017 Category: Research Authors: Chris MacDonald, Stanley Winistorfer, R. Marshall Pope, Michael E. Wright, Robert C. Piper Tags: TOOLBOX Source Type: research
