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https://www.readbyqxmd.com/read/29123131/influenza-virus-genome-reaches-the-plasma-membrane-via-a-modified-endoplasmic-reticulum-and-rab11-dependent-vesicles
#1
Isabel Fernández de Castro Martin, Guillaume Fournier, Martin Sachse, Javier Pizarro-Cerda, Cristina Risco, Nadia Naffakh
Transport of neo-synthesized influenza A virus (IAV) viral ribonucleoproteins (vRNPs) from the nucleus to the plasma membrane involves Rab 11 but the precise mechanism remains poorly understood. We used metal-tagging and immunolabeling to visualize viral proteins and cellular endomembrane markers by electron microscopy of IAV-infected cells. Unexpectedly, we provide evidence that the vRNP components and the Rab11 protein are present at the membrane of a modified, tubulated endoplasmic reticulum (ER) that extends all throughout the cell, and on irregularly coated vesicles (ICVs)...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29061883/kif13a-mediates-influenza-a-virus-ribonucleoproteins-trafficking
#2
Ana Ramos-Nascimento, Bárbara Kellen, Filipe Ferreira, Marta Alenquer, Silvia Vale-Costa, Graça Raposo, Cédric Delevoye, Maria João Amorim
Influenza A is a rapid evolving virus, successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite segmented genome of RNA (in the form of viral ribonucleoproteins, vRNPs). Genome assembly, with implications to public health, is not completely understood. It was reported that vRNPs are transported to the cell surface on Rab11 vesicles using microtubules, but no molecular motor has been assigned to the process. Here, we have identified KIF13A, a member of the kinesin-3 family, as the first molecular motor efficiently transporting vRNP-Rab11 vesicles during IAV infection...
October 23, 2017: Journal of Cell Science
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
#3
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
#4
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/29054881/ablation-of-tfr1-in-purkinje-cells-inhibits-mglu1-trafficking-and-impairs-motor-coordination-but-not-autistic-like-behaviors
#5
Jia-Huan Zhou, Xin-Tai Wang, Liang Zhou, Lin Zhou, Fang-Xiao Xu, Li-Da Su, Hao Wang, Fan Jia, Fu-Qiang Xu, Gui-Quan Chen, Chris De Zeeuw, Ying Shen
Group 1 metabotropic glutamate receptors (mGlu1/5) are critical to synapse formation and participate in synaptic long-term potentiation (LTP) and long-term depression (LTD) in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a trans-membrane protein of clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29028801/docrl-maintains-immune-cell-quiescence-by-regulating-endosomal-traffic
#6
Steven J Del Signore, Sarah A Biber, Katherine S Lehmann, Stephanie R Heimler, Benjamin H Rosenfeld, Tania L Eskin, Sean T Sweeney, Avital A Rodal
Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29020629/differential-regulation-of-lipoprotein-and-hepatitis-c-virus-secretion-by-rab1b
#7
Constantin N Takacs, Ursula Andreo, Viet Loan Dao Thi, Xianfang Wu, Caroline E Gleason, Michelle S Itano, Gabriella S Spitz-Becker, Rachel L Belote, Brenna R Hedin, Margaret A Scull, Charles M Rice, Sanford M Simon
Secretory cells produce diverse cargoes, yet how they regulate concomitant secretory traffic remains insufficiently explored. Rab GTPases control intracellular vesicular transport. To map secretion pathways, we generated a library of lentivirus-expressed dominant-negative Rab mutants and used it in a large-scale screen to identify regulators of hepatic lipoprotein secretion. We identified several candidate pathways, including those mediated by Rab11 and Rab8. Surprisingly, inhibition of Rab1b, the major regulator of transport from the endoplasmic reticulum to the Golgi, differently affected the secretion of the very-low-density lipoprotein components ApoE and ApoB100, despite their final association on mature secreted lipoprotein particles...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28979836/a-new-role-for-human-dyskerin-in-vesicular-trafficking
#8
Nunzia Di Maio, Rosario Vicidomini, Alberto Angrisani, Valentina Belli, Maria Furia, Mimmo Turano
Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X-linked dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. To further investigate the wide range of dyskerin's biological roles, we set up stable cell lines able to trigger inducible protein knockdown and allow a detailed analysis of the cascade of events occurring within a short time frame. We report that dyskerin depletion quickly induces cytoskeleton remodeling and significant alterations in endocytic Ras-related protein Rab-5A/Rab11 trafficking...
October 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28979185/the-membrane-glycoprotein-m6a-endocytic-recycling-pathway-involves-clathrin-mediated-endocytosis-and-affects-neuronal-synapses
#9
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/28945820/anthrax-edema-toxin-disrupts-distinct-steps-in-rab11-dependent-junctional-transport
#10
Annabel Guichard, Prashant Jain, Mahtab Moayeri, Ruth Schwartz, Stephen Chin, Lin Zhu, Beatriz Cruz-Moreno, Janet Z Liu, Bernice Aguilar, Andrew Hollands, Stephen H Leppla, Victor Nizet, Ethan Bier
Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28935671/efa6-regulates-selective-polarised-transport-and-axon-regeneration-from-the-axon-initial-segment
#11
Richard Eva, Hiroaki Koseki, Venkateswarlu Kanamarlapudi, James W Fawcett
Central nervous system (CNS) axons lose their intrinsic ability to regenerate with maturity, whilst peripheral (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their rab11 carriers. We reasoned that exclusion of the contents of rab11 vesicles including integrins might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this using laser axotomy...
September 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28931526/cellubrevin-vesicle-associated-membrane-protein-3-vamp-3-mediated-endocytosis-and-trafficking-regulate-platelet-functions
#12
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28926616/co-ordinated-activation-of-classical-and-novel-pkc-isoforms-is-required-for-pma-induced-mtorc1-activation
#13
Mengling Liu, Christopher J Clarke, Mohamed F Salama, Yeon Ja Choi, Lina M Obeid, Yusuf A Hannun
Protein kinase C (PKC) has been shown to activate the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, a central hub in the regulation of cell metabolism, growth and proliferation. However, the mechanisms by which PKCs activate mTORC1 are still ambiguous. Our previous study revealed that activation of classical PKCs (cPKC) results in the perinuclear accumulation of cPKC and phospholipase D2 (PLD2) in recycling endosomes in a PLD2-dependent manner. Here, we report that mTORC1 activation by phorbol 12,13-myristate acetate (PMA) requires both classic, cPKC, and novel PKC (nPKC) isoforms, specifically PKCη, acting through distinct pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28922401/rab11-family-expression-in-the-human-placenta-localization-at-the-maternal-fetal-interface
#14
Elizabeth S Taglauer, Patrycja A Artemiuk, Sara R Hanscom, Andrew J Lindsay, Danielle Wuebbolt, Fionnuala M Breathnach, Elizabeth C Tully, Amir R Khan, Mary W McCaffrey
Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28910396/pi3k-c2%C3%AE-knockdown-decreases-autophagy-and-maturation-of-endocytic-vesicles
#15
Nathan M Merrill, Joshua L Schipper, Jonathan B Karnes, Audra L Kauffman, Katie R Martin, Jeffrey P MacKeigan
Phosphoinositide 3-kinase (PI3K) family members are involved in diverse cellular fates including cell growth, proliferation, and survival. While many molecular details are known about the Class I and III PI3Ks, less is known about the Class II PI3Ks. To explore the function of all eight PI3K isoforms in autophagy, we knock down each gene individually and measure autophagy. We find a significant decrease in autophagy following siRNA-mediated PIK3C2A (encoding the Class 2 PI3K, PI3K-C2α) knockdown. This defective autophagy is rescued by exogenous PI3K-C2α, but not kinase-dead PI3K-C2α...
2017: PloS One
https://www.readbyqxmd.com/read/28902870/reduced%C3%A2-insulin-signaling-maintains-electrical-transmission-in-a-neural-circuit-in-aging-flies
#16
Hrvoje Augustin, Kieran McGourty, Marcus J Allen, Sirisha Kudumala Madem, Jennifer Adcott, Fiona Kerr, Chi Tung Wong, Alec Vincent, Tanja Godenschwege, Emmanuel Boucrot, Linda Partridge
Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the "insulin paradox"). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced...
September 2017: PLoS Biology
https://www.readbyqxmd.com/read/28874464/mas1-receptor-trafficking-involves-erk1-2-activation-through-a-%C3%AE-arrestin2-dependent-pathway
#17
Flavia M Cerniello, Oscar A Carretero, Nadia A Longo Carbajosa, Bruno D Cerrato, Robson A Santos, Hernán E Grecco, Mariela M Gironacci
The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein)...
November 2017: Hypertension
https://www.readbyqxmd.com/read/28857357/aspergillus-nidulans-baph-is-a-rab11-effector-that-connects-membranes-in-the-spitzenk%C3%A3-rper-with-basal-autophagy
#18
Mario Pinar, Miguel A Peñalva
Using affinity chromatography we identified the Aspergillus nidulans F-BAR-and-PH domain-containing protein BapH as a RabE(RAB11) effector. BapH localizes to the Spitzenkörper (SPK) in an F-actin- and Sec7-dependent manner, becoming cytosolic after inactivation of Trs120 in TRAPPII, the oligomeric GEF for RabE(RAB11) . Therefore, RabE(RAB11) contributes to the recruitment of BapH to secretory vesicles in vivo. BapH has a close homologue, SlmA, which is related to yeast Slm1p/Slm2p, localizes to eisosomes and does not bind RabE(RAB11) ...
November 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28829741/selective-rab11-transport-and-the-intrinsic-regenerative-ability-of-cns-axons
#19
Hiroaki Koseki, Matteo Donegá, Brian Yh Lam, Veselina Petrova, Susan van Erp, Giles Sh Yeo, Jessica Cf Kwok, Charles Ffrench-Constant, RIchard Eva, James W Fawcett
Neurons lose intrinsic axon regenerative ability with maturation, but the mechanism remains unclear. Using an in-vitro laser axotomy model, we show a progressive decline in the ability of cut CNS axons to form a new growth cone and then elongate. Failure of regeneration was associated with increased retraction after axotomy. Transportation into axons becomes selective with maturation; we hypothesized that selective exclusion of molecules needed for growth may contribute to regeneration decline. With neuronal maturity Rab11 vesicles (which carry many molecules involved in axon growth) became selectively targeted to the somatodendritic compartment and excluded from axons...
August 8, 2017: ELife
https://www.readbyqxmd.com/read/28739266/identification-of-%C3%AE-helix-4-%C3%AE-4-of-rab11a-as-a-novel-rab11-binding-domain-rbd-interaction-of-rab11a-with-the-prostacyclin-receptor
#20
Eamon P Mulvaney, Fergal O'Meara, Amir R Khan, David J O'Connell, B Therese Kinsella
The cellular trafficking of numerous G protein-coupled receptors (GPCRs) is known to be regulated by Rab proteins that involves a direct protein:protein interaction between the receptor and the GTPase. In the case of the human prostacyclin receptor (hIP), it undergoes agonist-induced internalization and subsequent Rab11a-dependent recyclization involving an interaction between a Rab11-binding domain (RBD) localized within its carboxyl-tail domain with Rab11a. However, the GPCR-interacting domain on Rab11a itself is unknown...
July 22, 2017: Biochimica et Biophysica Acta
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