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https://www.readbyqxmd.com/read/28550201/the-influence-of-mhc-class-ii-on-b-cell-defects-induced-by-invariant-chain-cd74-n-terminal-fragments
#1
Janna Schneppenheim, Ann-Christine Loock, Susann Hüttl, Michaela Schweizer, Renate Lüllmann-Rauch, Hans-Heinrich Oberg, Philipp Arnold, Christian H K Lehmann, Diana Dudziak, Dieter Kabelitz, Ralph Lucius, Ana-Maria Lennon-Duménil, Paul Saftig, Bernd Schröder
The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a(-/-) B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550150/cellulose-synthesis-and-cell-expansion-are-regulated-by-different-mechanisms-in-growing-arabidopsis-hypocotyls
#2
Alexander A Ivakov, Anna Flis, Federico Apelt, Maximilian Fuenfgeld, Ulrike Scherer, Mark Stitt, Friedrich Kragler, Kris Vissenberg, Staffan Persson, Dmitry Suslov
Plant growth is sustained by two complementary processes - biomass biosynthesis and cell expansion. The cell wall is crucial to both as it forms the majority of biomass, while its extensibility limits cell expansion. Cellulose is a major component of the cell wall and cellulose synthesis is pivotal to plant cell growth and its regulation is poorly understood. Using periodic diurnal variation in Arabidopsis thaliana hypocotyl growth, we found that cellulose synthesis and cell expansion can be uncoupled and are regulated by different mechanisms...
May 26, 2017: Plant Cell
https://www.readbyqxmd.com/read/28550110/trpm8-inhibits-endothelial-cell-migration-via-a-non-channel-function-by-trapping-the-small-gtpase-rap1
#3
Tullio Genova, Guillaume P Grolez, Chiara Camillo, Michela Bernardini, Alexandre Bokhobza, Elodie Richard, Marco Scianna, Loic Lemonnier, Donatella Valdembri, Luca Munaron, Mark R Philips, Virginie Mattot, Guido Serini, Natalia Prevarskaya, Dimitra Gkika, Alessandra Fiorio Pla
Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown. Here, we reveal a novel non-channel function for TRPM8 that unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting endothelial cell motility, independently of pore function...
May 26, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28550066/rapid-whole-genome-sequencing-identifies-a-novel-homozygous-npc1-variant-associated-with-niemann-pick-type-c1-disease-in-a-7-week-old-male-with-cholestasis
#4
Amber Hildreth, Kristen Wigby, Shimul Chowdhury, Shareef Nahas, Jaime Barea, Paulina Ordonez, Serge Batalov, David M Dimmock, Rcigm Investigators, Stephen F Kingsmore
Niemann-Pick Type C disease (NPC; OMIM #257220) is an inborn error of intracellular cholesterol trafficking. It is an autosomal recessive disorder caused predominantly by mutations in NPC1. While characterized as a progressive neurological disorder, it can also cause cholestasis and liver dysfunction due to intrahepatocyte lipid accumulation. We report a 7 week old who was admitted with neonatal cholestasis, who was diagnosed with a novel homozygous stop-gain variant in NPC1 by rapid whole genome sequencing (WGS)...
May 26, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28550053/batf3-dendritic-cells-drive-adoptive-effector-t-cell-trafficking
#5
(no author information available yet)
Trafficking of adoptively transferred effector T cells requires CD103(+) dendritic cell-derived CXCL9/10.
May 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28550045/pacsin2-accelerates-nephrin-trafficking-and-is-up-regulated-in-diabetic-kidney-disease
#6
Vincent Dumont, Tuomas A Tolvanen, Sara Kuusela, Hong Wang, Tuula A Nyman, Sonja Lindfors, Jukka Tienari, Harry Nisen, Shiro Suetsugu, Markus Plomann, Hiroshi Kawachi, Sanna Lehtonen
Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker Diabetic Fatty (ZDF) rats that have altered renal function...
May 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28549691/27-hydroxycholesterol-upregulates-the-production-of-heat-shock-protein-60-of-monocytic-cells
#7
Bo-Young Kim, Yonghae Son, Jeongyoon Choi, Seong-Kug Eo, Young Chul Park, Koanhoi Kim
Investigating differentially expressed proteins in a milieu rich in cholesterol oxidation products, we found via mass spectrometry-based proteomics that surface levels of heat shock protein 60 (HSP60) were upregulated on monocytic cells in the presence of 27-hydroxycholesterol (27OHChol). The elevated levels of cytoplasmic membrane HSP60 were verified via Western blot analysis and visualized by confocal microscopy. Treatment with 27OHChol also resulted in increased levels of cellular HSP60 without altering its transcription...
May 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28549545/developmental-and-internal-validation-of-a-novel-13-loci-str-multiplex-method-for-cannabis-sativa-dna-profiling
#8
Rachel Houston, Matthew Birck, Sheree Hughes-Stamm, David Gangitano
Marijuana (Cannabis sativa L.) is a plant cultivated and trafficked worldwide as a source of fiber (hemp), medicine, and intoxicant. The development of a validated method using molecular techniques such as short tandem repeats (STRs) could serve as an intelligence tool to link multiple cases by means of genetic individualization or association of cannabis samples. For this purpose, a 13 loci STR multiplex method was developed, optimized, and validated according to relevant ISFG and SWGDAM guidelines. The STR multiplex consists of 13 previously described C...
May 2017: Legal Medicine
https://www.readbyqxmd.com/read/28549128/atad3-gene-cluster-deletions-cause-cerebellar-dysfunction-associated-with-altered-mitochondrial-dna-and-cholesterol-metabolism
#9
Radha Desai, Ann E Frazier, Romina Durigon, Harshil Patel, Aleck W Jones, Ilaria Dalla Rosa, Nicole J Lake, Alison G Compton, Hayley S Mountford, Elena J Tucker, Alice L R Mitchell, Deborah Jackson, Abdul Sesay, Miriam Di Re, Lambert P van den Heuvel, Derek Burke, David Francis, Sebastian Lunke, George McGillivray, Simone Mandelstam, Fanny Mochel, Boris Keren, Claude Jardel, Anne M Turner, P Ian Andrews, Jan Smeitink, Johannes N Spelbrink, Simon J Heales, Masakazu Kohda, Akira Ohtake, Kei Murayama, Yasushi Okazaki, Anne Lombès, Ian J Holt, David R Thorburn, Antonella Spinazzola
Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and are among the most common neurogenetic disorders. Identifying the causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once the defect is known, researchers face the challenge of deciphering the underlying disease mechanism. Here we characterize large biallelic deletions in the region encoding the ATAD3C, ATAD3B and ATAD3A genes. Although high homology complicates genomic analysis of the ATAD3 defects, they can be identified by targeted analysis of standard single nucleotide polymorphism array and whole exome sequencing data...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28548451/molecular-and-functional-characterization-of-the-american-cockroach-periplaneta-americana-rab5-the-first-exopterygotan-low-molecular-weight-ovarian-gtpase-during-oogenesis
#10
Mohamed Elmogy, Amr A Mohamed, Muhammad Tufail, Tomohide Uno, Makio Takeda
The small Rab GTPases are key regulators of membrane vesicle trafficking. Ovaries of Periplaneta americana (Linnaeus) (Blattodea: Blattidae) have small molecular weight GTP/ATP-binding proteins during early and late vitellogenic periods of oogenesis. However, the identification and characterization of the detected proteins have not been yet reported. Herein, we cloned a cDNA encoding Rab5 from the American cockroach, P. americana, ovaries (PamRab5). It comprises 796 bp, encoding a protein of 213 amino acid residues with a predicted molecular weight of 23...
May 26, 2017: Insect Science
https://www.readbyqxmd.com/read/28547795/synaptogenesis-and-synaptic-protein-localization-in-the-postnatal-development-of-rod-bipolar-cell-dendrites-in-mouse-retina
#11
Zvan A Anastassov, Weiwei Wang, Felice A Dunn
Retinal responses to photons originate in rod photoreceptors and are transmitted to the ganglion cell output of the retina through the primary rod bipolar pathway. At the first synapse of this pathway, input from multiple rods is pooled into individual rod bipolar cells. This architecture is called convergence. Convergence serves to improve sensitivity of rod vision when photons are sparse. Establishment of convergence depends on the development of a proper complement of dendritic tips and transduction proteins in rod bipolar cells...
May 25, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28546853/caveolin-1-an-oxidative-stress-related-target-for-cancer-prevention
#12
REVIEW
Shengqi Wang, Neng Wang, Yifeng Zheng, Jin Zhang, Fengxue Zhang, Zhiyu Wang
Aberrant oxidative metabolism is one of the hallmarks of cancer. Reactive species overproduction could promote carcinogenesis via inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy was considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, has been shown to mediate tumorigenesis and progression through oxidative stress modulation recently. Reactive species could modulate the expression, degradation, posttranslational modifications, and membrane trafficking of Cav-1, while Cav-1-targeted treatments could scavenge the reactive species...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28546447/signal-motifs-dependent-er-export-of-qc-snare-bet12-interacts-with-memb12-and-affects-pr1-trafficking-in-arabidopsis
#13
Kin Pan Chung, Yonglun Zeng, Yimin Li, Changyang Ji, Yiji Xia, Liwen Jiang
SNAREs are well-known for their role in controlling membrane fusion, the final but crucial step for vesicular transport in eukaryotes. SNARE proteins contribute to various biological processes including pathogen defense, channel activity regulation as well as plant growth and development. Precise targeting of SNARE proteins to destined compartments is a prerequisite for their proper functioning. However, the underlying mechanism(s) for SNAREs targeting in plants remains obscure. Here we investigate the targeting mechanism of the Qc-SNARE BET12, which is involved in protein trafficking in the early secretory pathway...
May 25, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28546340/the-golgi-matrix-protein-giantin-is-required-for-normal-cilia-function-in-zebrafish
#14
Dylan J M Bergen, Nicola L Stevenson, Roderick E H Skinner, David J Stephens, Christina L Hammond
The Golgi is essential for glycosylation of newly synthesised proteins including almost all cell-surface and extracellular matrix proteoglycans. Giantin, encoded by the golgb1 gene, is a member of the golgin family of proteins that reside within the Golgi stack but its function remains elusive. Loss-of-function of giantin in rats causes osteochondrodysplasia; knockout mice show milder defects, notably a cleft palate. In vitro, giantin has been implicated in Golgi organisation, biosynthetic trafficking, and ciliogenesis...
May 25, 2017: Biology Open
https://www.readbyqxmd.com/read/28546101/an-efficient-and-cost-effective-method-of-generating-postnatal-p2-5-mouse-primary-hippocampal-neuronal-cultures
#15
A Kaar, S J Morley, M G Rae
BACKGROUND: Primary culture of postnatal central neurons is a widely used methodology for applications such as the investigation of neuronal development, protein trafficking/distribution and cellular signalling. However, successful production and maintenance of such cultures, particularly from postnatal animals, can be challenging. In attempting to surmount these difficulties, several disparate culturing methodologies have been developed. Such methodologies are centred on the identification and optimisation of critical steps and, as such, the protocols and reagents utilised can differ quite markedly from protocol to protocol, often with the suggestion that the use of a (usually expensive) proprietary reagent(s), lengthy substrate preparation and/or cell isolation techniques is/are necessary for successful culture preparation...
May 22, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28546080/exosomes-in-hiv-infection-a-review-and-critical-look
#16
REVIEW
Joel Henrique Ellwanger, Tiago Degani Veit, José Artur Bogo Chies
Exosomes are nanovesicles released into the extracellular medium by different cell types. These vesicles carry a variety of protein and RNA cargos, and have a central role in cellular signaling and regulation. A PubMed search using the term "exosomes" finds 67 articles published in 2006. Ten years later, the same search returns approximately 1200 results for 2016 alone. The growing interest in exosomes within the scientific community reflects the different roles exerted by extracellular vesicles in biological systems and diseases...
May 22, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28545594/early-blockade-of-joint-inflammation-with-a-fatty-acid-amide-hydrolase-inhibitor-decreases-end-stage-osteoarthritis-pain-and-peripheral-neuropathy-in-mice
#17
Jason J McDougall, Milind M Muley, Holly T Philpott, Allison Reid, Eugene Krustev
BACKGROUND: The endocannabinoid system has been shown to reduce inflammatory flares and pain in rodent models of arthritis. A limitation of endocannabinoids is that they are rapidly denatured by hydrolysing enzymes such as fatty acid amide hydrolase (FAAH) which renders them physiologically inert. Osteoarthritis (OA) is primarily a degenerative joint disease; however, it can incorporate mild inflammation and peripheral neuropathy. The aim of this study was to determine whether early blockade of FAAH bioactivity could reduce OA-associated inflammation and joint neuropathy...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#18
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544880/systems-wide-studies-uncover-commander-a-multiprotein-complex-essential-to-human-development
#19
REVIEW
Anna L Mallam, Edward M Marcotte
Recent mass spectrometry maps of the human interactome independently support the existence of a large multiprotein complex, dubbed "Commander." Broadly conserved across animals and ubiquitously expressed in nearly every human cell type examined thus far, Commander likely plays a fundamental cellular function, akin to other ubiquitous machines involved in expression, proteostasis, and trafficking. Experiments on individual subunits support roles in endosomal protein sorting, including the trafficking of Notch proteins, copper transporters, and lipoprotein receptors...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544744/structural-basis-for-copper-oxygen-mediated-c-h-bond-activation-by-the-formylglycine-generating-enzyme
#20
Marcel Meury, Matthias Knop, Florian P Seebeck
The formylglycine-generating enzyme (FGE) is a unique copper-protein that catalyzes oxygen-dependent C-H activation. We describe 1.66 Å- and 1.28 Å-resolution crystal structures of FGE from Thermomonospora curvata in complex with either Ag (I) or Cd (II) providing definitive evidence for a high-affinity metal-binding site in this enzyme. The structures reveal a bis-cysteine linear coordination of the monovalent metal, and tetrahedral coordination of the bivalent metal. Similar coordinational change may occur in the active enzyme as a result of Cu (I)/(II) redox cycling...
May 22, 2017: Angewandte Chemie
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