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https://www.readbyqxmd.com/read/29025970/the-arf-gef-gbf1-and-arf4-synergize-with-the-sensory-receptor-cargo-rhodopsin-to-regulate-ciliary-membrane-trafficking
#1
Jing Wang, Theresa Fresquez, Vasundhara Kandachar, Dusanka Deretic
The small GTPase Arf4 and the Arf GTPase activating protein (GAP) ASAP1 cooperatively sequester sensory receptor cargo into transport carriers targeted to primary cilia, but the input that drives Arf4 activation in this process remains unknown. Here, we show that during the carrier biogenesis from the photoreceptor Golgi/trans-Golgi network (TGN) a functional complex is formed between Arf4, the Arf guanine nucleotide exchange factor (GEF) GBF1 and the light-sensing receptor, rhodopsin. Rhodopsin and Arf4 bind the regulatory N-terminal DCB-HUS domain of GBF1...
October 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29024759/specificity-of-plant-membrane-trafficking-arfs-regulators-and-coat-proteins
#2
REVIEW
Manoj K Singh, Gerd Jürgens
Approximately one-third of all eukaryotic proteins are delivered to their destination by trafficking within the endomembrane system. Such cargo proteins are incorporated into forming membrane vesicles on donor compartments and delivered to acceptor compartments by vesicle fusion. How cargo proteins are sorted into forming vesicles is still largely unknown. Here we review the roles of small GTPases of the ARF/SAR1 family, their regulators designated ARF guanine-nucleotide exchange factors (ARF-GEFs) and ARF GTPase-activating proteins (ARF-GAPs) as well as coat protein complexes during membrane vesicle formation...
October 9, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29024643/gbps-inhibit-motility-of-shigella-flexneri-but-are-targeted-for-degradation-by-the-bacterial-ubiquitin-ligase-ipah9-8
#3
Michal P Wandel, Claudio Pathe, Emma I Werner, Cara J Ellison, Keith B Boyle, Alexander von der Malsburg, John Rohde, Felix Randow
Interferon exposure boosts cell-autonomous immunity for more efficient pathogen control. But how interferon-enhanced immunity protects the cytosol against bacteria and how professionally cytosol-dwelling bacteria avoid clearance are insufficiently understood. Here we demonstrate that the interferon-induced GTPase family of guanylate-binding proteins (GBPs) coats Shigella flexneri in a hierarchical manner reliant on GBP1. GBPs inhibit actin-dependent motility and cell-to-cell spread of bacteria but are antagonized by IpaH9...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29024508/importance-of-an-orchestrate-participation-of-each-individual-residue-present-at-a-catalytic-site
#4
Santanu Das
GTP hydrolysis is indispensable to keep a living cell healthy. Nature has evolved so many enzymes to enhance the slow GTP hydrolysis. Rab GTPases are evolved to regulate vesicle trafficking. GTPase activating proteins (GAPs) accelerates their intrinsic slow GTP hydrolysis in order to maintain the sustainability between cellular events. Any malfunction/interference in this hydrolysis disrupts normal cellular events and causes severe diseases. In this study, GTP hydrolysis mechanism of Rab33B catalyzed by TBC-domain GAP protein Gyp1p has been decoded using extensive ab initio QM/MM metadynamics simulations...
October 12, 2017: Molecular Informatics
https://www.readbyqxmd.com/read/29024245/hace1-influences-zebrafish-cardiac-development-via-ros-dependent-mechanisms
#5
Babak Razaghi, Shelby L Steele, Sergey V Prykhozhij, Matthew R Stoyek, Jessica A Hill, Matthew D Cooper, Lindsay McDonald, William Lin, Mads Daugaard, Nicolas Crapoulet, Simi Chacko, Stephen Lewis, Ian C Scott, Poul H B Sorensen, Jason N Berman
BACKGROUND: In this study we reveal a previously undescribed role of the HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) tumor suppressor protein in normal vertebrate heart development using the zebrafish (Danio rerio) model. We examined the link between the cardiac phenotypes associated with hace1 loss of function to the expression of the Rho small family GTPase, rac1, which is a known target of HACE1 and promotes ROS production via its interaction with NADPH oxidase holoenzymes...
October 11, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29022905/c-abl-mediated-drp1-phosphorylation-promotes-oxidative-stress-induced-mitochondrial-fragmentation-and-neuronal-cell-death
#6
Lujun Zhou, Qiang Zhang, Peng Zhang, Lei Sun, Can Peng, Zengqiang Yuan, Jinbo Cheng
Oxidative stress-induced mitochondrial dysfunction and neuronal cell death have important roles in the development of neurodegenerative diseases. Dynamin related protein 1 (Drp1) is a critical factor in regulating mitochondrial dynamics. A variety of posttranslational modifications of Drp1 have been reported, including phosphorylation, ubiquitination, sumoylation and S-nitrosylation. In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022874/uncoupling-of-dynamin-polymerization-and-gtpase-activity-revealed-by-the-conformation-specific-nanobody-dynab
#7
Valentina Galli, Rafael Sebastian, Sandrine Moutel, Jason Ecard, Franck Perez, Aurélien Roux
Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (1, 2). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (3): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1...
October 12, 2017: ELife
https://www.readbyqxmd.com/read/29022003/data-on-the-effect-of-knockout-of-cytohesin-1-in-myelination-related-protein-kinase-signaling
#8
Ruri Tsuneishi, Naoto Matsumoto, Misa Itaoka, Yuri Urai, Minami Kaneko, Natsumi Watanabe, Shou Takashima, Yoichi Seki, Takako Morimoto, Hiroyuki Sakagami, Yuki Miyamoto, Junji Yamauchi
Cytohesin-1 is the guanine-nucleotide exchange factor of Arf6, a small GTPase of Arf family, and participates in cellular morphological changes. Knockout mice of cytohesin-1 exhibit decreased myelination of neuronal axons in the peripheral nervous system (PNS) "Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2012) [1]". Herein we provide the data regarding decreased phosphorylation levels of protein kinases involved in two major myelination-related kinase cascades in cytohesin-1 knockout mice...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29020629/differential-regulation-of-lipoprotein-and-hepatitis-c-virus-secretion-by-rab1b
#9
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/29017772/t-cell-activation-rho-gtpase-activating-protein-tagap-is-upregulated-in-clinical-and-experimental-arthritis
#10
Maria Arshad, Attya Bhatti, Peter John, Fazal Jalil, Federica Borghese, Joanna Z Kawalkowska, Richard O Williams, Felix I L Clanchy
Genome-wide association studies have identified various susceptibility variants and loci associated with incidence of rheumatoid arthritis (RA) in different populations. One of these is T cell activation Rho GTPase activating protein (TAGAP). The present study sought to measure the expression of TAGAP in RA patients, CD4(+) T cells subsets from healthy humans and in mice with collagen-induced arthritis. Peripheral blood mononuclear cells (PBMC) from RA patients and tissues of arthritic mice at different stages of the disease were used for the evaluation of TAGAP mRNA expression...
October 7, 2017: Cytokine
https://www.readbyqxmd.com/read/29016873/cgnl1-an-endothelial-junction-complex-protein-regulates-gtpase-mediated-angiogenesis
#11
Ihsan Chrifi, Dorien Hermkens, Maarten M Brandt, Christian G M van Dijk, Petra E Bürgisser, Remco Haasdijk, Jiayi Pei, Esther H M van de Kamp, Changbin Zhu, Lau Blonden, Johan M Kros, Dirk J Duncker, Henricus J Duckers, Caroline Cheng
Aims: The formation of cell-cell and cell-extra cellular matrix contacts by endothelial cells is crucial for the stability and integrity of a vascular network. We previously identified cingulin-like 1 (Cgnl1) in a transcriptomic screen for new angiogenic modulators. Here we aim to study the function of the cell-cell junction associated protein Cgnl1 during vessel formation. Methods and Results: Unlike family member cingulin, Cgnl1 expression is enriched in endothelial cells during vascular growth...
August 31, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29016860/primary-angle-closure-glaucoma-pacg-susceptibility-gene-plekha7-encodes-a-novel-rac1-cdc42-gap-that-modulates-cell-migration-and-blood-aqueous-barrier-function
#12
Mei-Chin Lee, William Shei, Anita S Chan, Boon-Tin Chua, Shuang-Ru Goh, Yaan-Fun Chong, Maryam H Hilmy, Monisha E Nongpiur, Mani Baskaran, Chiea-Chuen Khor, Tin Aung, Walter Hunziker, Eranga N Vithana
PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29016458/quantitative-analysis-of-hyperautofluorescent-rings-to-characterize-the-natural-history-and-progression-in-rpgr-associated-retinopathy
#13
James J L Tee, Angelos Kalitzeos, Andrew R Webster, Tunde Peto, Michel Michaelides
PURPOSE: Quantitative analysis of hyperautofluorescent rings and progression in subjects with retinitis pigmentosa associated with retinitis pigmentosa GTPase regulator (RPGR) gene mutations. METHODS: Prospective observational study of 46 subjects. Ring area, horizontal and vertical diameter measurements taken from outer and inner ring borders. Intraobserver repeatability, baseline measurements, progression rates, interocular symmetry, and association with age and genotype were investigated...
October 6, 2017: Retina
https://www.readbyqxmd.com/read/29016307/the-differential-expression-and-possible-function-of-long-noncoding-rnas-in-liver-cells-infected-by-dengue-virus
#14
Xiao-Jun Wang, Shi-Chen Jiang, Hai-Xia Wei, Sheng-Qun Deng, Cheng He, Hong-Juan Peng
The function of long noncoding RNAs (lncRNAs) in liver injury resulted by dengue virus (DENV) infection have not yet been explored. The differential expression profiles of lncRNAs coupled with mRNAs in L-02 liver cells in the DENV1 infected, DENV2 infected, and untreated control group were analyzed after high throughput RNA sequencing, the significantly upregulated and downregulated lncRNAs or mRNAs comparing with the control group were identified with a cutoff value at log2 (ratio) ≥ 1.5 and log2 (ratio) ≤ -1...
October 2, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28993468/a-ragulator-borc-interaction-controls-lysosome-positioning-in-response-to-amino-acid-availability
#15
Jing Pu, Tal Keren-Kaplan, Juan S Bonifacino
Lysosomes play key roles in the cellular response to amino acid availability. Depletion of amino acids from the medium turns off a signaling pathway involving the Ragulator complex and the Rag guanosine triphosphatases (GTPases), causing release of the inactive mammalian target of rapamycin complex 1 (mTORC1) serine/threonine kinase from the lysosomal membrane. Decreased phosphorylation of mTORC1 substrates inhibits protein synthesis while activating autophagy. Amino acid depletion also causes clustering of lysosomes in the juxtanuclear area of the cell, but the mechanisms responsible for this phenomenon are poorly understood...
October 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28993397/graf-regulates-hematopoiesis-through-geec-endocytosis-of-egfr
#16
Sungdae Kim, Minyeop Nahm, Najin Kim, Yumi Kwon, Joohyung Kim, Sukwoo Choi, Eun Young Choi, Jiwon Shim, Cheolju Lee, Seungbok Lee
GTPase regulator associated with focal adhesion kinase-1 (Graf1) is an essential component of the GPI-enriched endocytic compartment (GEEC) endocytosis pathway. Mutations in the human graf1 gene are associated with acute myeloid leukemia (AML), but its normal role in myeloid cell development remains unclear. We show that Graf, the Drosophila ortholog of Graf1, is expressed and specifically localizes to GEEC endocytic membranes in macrophage-like plasmatocytes. We also find that loss of Graf impairs GEEC endocytosis, enhances EGFR signaling, and induces a plasmatocyte overproliferation phenotype that requires the EGFR signaling cascade...
October 9, 2017: Development
https://www.readbyqxmd.com/read/28990524/statins-and-inflammation-in-cardiovascular-disease
#17
Georgia Vogiatzi, Evangelos Oikonomou, Gerasimos Siasos, Sotiris Tsalamandris, Alexandros Briasoulis, Emmanuel Androulakis, George Latsios, Spyridon Papaioannou, Konstantinos Tsioufis, Dimitris Tousoulis
BACKGROUND: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction...
October 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28986221/the-ul10-protein-a-component-of-the-ribosomal-p-stalk-is-released-from-the-ribosome-in-nucleolar-stress
#18
Kamil Deryło, Barbara Michalec-Wawiórka, Dawid Krokowski, Leszek Wawiórka, Maria Hatzoglou, Marek Tchórzewski
The ribosomal uL10 protein, formerly known as P0, is an essential element of the ribosomal GTPase-associated center responsible for the interplay with translational factors during various stages of protein synthesis. In eukaryotic cells, uL10 binds two P1/P2 protein heterodimers to form a pentameric P-stalk, described as uL10-(P1-P2)2, which represents the functional form of these proteins on translating ribosomes. Unlike most ribosomal proteins, which are incorporated into pre-ribosomal particles during early steps of ribosome biogenesis in the nucleus, P-stalk proteins are attached to the 60S subunit in the cytoplasm...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28984774/a-case-report-of-tongue-metastasis-from-lung-squamous-cell-carcinoma-and-literature-review
#19
REVIEW
Xiaolong Cheng, Zhenli Hu, Yipin Han, Chong Bai
RATIONALE: Tongue metastasis from lung cancer is extremely rare, and the prognosis of these patients is rather poor. PATIENT CONCERS: A 56-year-old man was found a 4-cm cavity lesion in the left upper lobe, which was initially misdiagnosed as tuberculosis. DIAGNOSES: A case of lung squamous cell carcinoma that metastasized to the base of a patient's tongue. INTERVATIONS: We send the biopsy of the lung and the tongue lesions for gene sequencing...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28983640/a-haplotypic-variant-at-the-irgm-locus-and-rs11747270-are-related-to-the-susceptibility-for-chronic-periodontitis
#20
Matthias Folwaczny, Eleni Tsekeri, Jürgen Glas
OBJECTIVE AND DESIGN: Immunity-regulated GTPase M (IRGM) plays a critical role in the defense against intracellular bacteria by regulating autophagy formation. This direct genetic association study aimed to determine whether variants at the IRGM genetic locus are associated with chronic periodontitis. MATERIALS AND SUBJECTS: Using PCR and melting curve analysis 390 periodontitis patients and 770 healthy controls have been genotyped regarding six polymorphisms in the IRGM gene (rs13361189, rs10065172, rs4958847, rs1000113, rs11747270, rs931058)...
October 5, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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