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https://www.readbyqxmd.com/read/29458182/a-direct-gateway-into-the-extracellular-space-unconventional-secretion-of-fgf2-through-self-sustained-plasma-membrane-pores
#1
REVIEW
Julia P Steringer, Walter Nickel
As illustrated by a diverse set of examples in this special issue, multiple mechanisms of protein secretion have been identified in eukaryotes that do not involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most prominent example. Unconventional secretion of FGF2 from cells is mediated by direct protein translocation across the plasma membrane. A unique feature of this process is the ability of FGF2 to form its own membrane translocation intermediate through oligomerization and membrane insertion...
February 16, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29455446/big2-arf1-rhoa-mdia1-signaling-regulates-dendritic-golgi-polarization-in-hippocampal-neurons
#2
Eun-Hye Hong, Ji-Ye Kim, Jeong-Hoon Kim, Dae-Sik Lim, Minkyu Kim, Jeong-Yoon Kim
Proper dendrite development is essential for establishing neural circuitry, and Rho GTPases play key regulatory roles in this process. From mouse brain lysates, we identified Brefeldin A-inhibited guanine exchange factor 2 (BIG2) as a novel Rho GTPase regulatory protein involved in dendrite growth and maintenance. BIG2 was highly expressed during early development, and knockdown of the ARFGEF2 gene encoding BIG2 significantly reduced total dendrite length and the number of branches. Expression of the constitutively active ADP-ribosylation factor 1 ARF1 Q71L rescued the defective dendrite morphogenesis of ARFGEF2-null neurons, indicating that BIG2 controls dendrite growth and maintenance by activating ARF1...
February 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29455434/elucidating-post-translational-regulation-of-mouse-creb3-in-neuro2a-cells
#3
Kentaro Oh-Hashi, Ayano Soga, Yoshihisa Naruse, Kanto Takahashi, Kazutoshi Kiuchi, Yoko Hirata
CREB3 is an ER membrane-bound transcription factor; however, post-translational regulation of CREB3, including expression, processing, and activation, is not fully characterized. We therefore constructed several types of mouse CREB3 expression genes and elucidated their expression in Neuro2a cells by treatment with stimuli and co-transfection with genes associated with ER-Golgi homeostasis, such as mutant Sar1 [H79G], GRP78, and KDEL receptor 1 (KDELR1). Interestingly, treatment of Neuro2a cells expressing Flag-tagged full-length CREB3 with monensin and nigericin induced the expression of the approximately 50 kDa N-terminal fragment; however, its cleavage was not parallel to the levels of GADD153 and LC3-II...
February 17, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29454964/nek3-mediated-snap29-phosphorylation-modulates-its-membrane-association-and-snare-fusion-dependent-processes
#4
Debora Rapaport, Boris Fichtman, Hilla Weidberg, Eli Sprecher, Mia Horowitz
Intracellular membrane fusion depends on the presence of specific mediators, the vesicle (v-) and the target (t-) SNAREs (Soluble N-ethylmaleimide-sensitive factor, NSF, attachment protein SNAP receptors), whose interaction brings apposing membranes to close proximity and initiates their fusion. SNAP29 (synaptosomal-associated protein 29), a t-SNARE protein, is involved in multiple fusion events during intracellular transport and affects structure of organelles such as the Golgi apparatus and focal adhesions...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29450800/the-endogenous-subcellular-localisations-of-the-long-chain-fatty-acid-activating-enzymes-acsl3-and-acsl4-in-sarcoma-and-breast-cancer-cells
#5
Yassmeen Radif, Haarith Ndiaye, Vasiliki Kalantzi, Ruth Jacobs, Andrew Hall, Shane Minogue, Mark G Waugh
Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype...
February 15, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29446202/conditional-deletion-of-cadherin-13-perturbs-golgi-cells-and-disrupts-social-and-cognitive-behaviors
#6
Martesa Tantra, Lanboling Guo, Jinsook Kim, Norliyana Zainolabidin, George J Augustine, Volker Eulenburg, Albert I Chen
Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebelluar cortex...
February 15, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29445937/secondary-hemophagocytic-syndrome-associated-with-cog6-gene-defect-report-and-review
#7
Nouf Althonaian, Abdulrahman Alsultan, Eva Morava, Majid Alfadhel
Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease that is characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes. Clinically, it is characterized by prolonged fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, pancytopenia, and hemophagocytosis in the bone marrow, spleen, or lymph nodes. It can be classified as primary if it is due to a genetic defect, or secondary if it is due to a different etiology such as severe infection, immune deficiency syndrome, rheumatological disorder, malignancy, and inborn errors of metabolism such as galactosemia, multiple sulfatase deficiency, lysinuric protein intolerance, Gaucher disease, Niemann-Pick disease, Wolman disease, propionic acidemia, methylmalonic acidemia, biotinidase deficiency, cobalamin C defect, galactosialidosis, Pearson syndrome, and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency...
February 15, 2018: JIMD Reports
https://www.readbyqxmd.com/read/29444945/interaction-of-human-cytomegalovirus-tegument-proteins-ppul35-and-ppul35a-with-sorting-nexin-5-regulates-glycoprotein-b-gpul55-localization
#8
Gregor Maschkowitz, Sabine Gärtner, Heike Hofmann-Winkler, Helmut Fickenscher, Michael Winkler
Human cytomegalovirus (HCMV) is a wide-spread human pathogen that causes asymptomatic infection in healthy individuals, but poses a serious threat to immunocompromised patients. During the late phase of HCMV infection, the viral capsid is transported to the cytoplasmic viral assembly center (cVAC) where it is enclosed by the tegument protein layer and the viral envelope. The cVAC consists of circularly arranged vesicles from the trans-Golgi and endosomal networks. The HCMV gene UL35 encodes ppUL35 and its shorter form ppUL35A...
February 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29444177/kidney-differentiated-cells-derived-from-lowe-syndrome-patient-s-ipscs-show-ciliogenesis-defects-and-six2-retention-at-the-golgi-complex
#9
Wen-Chieh Hsieh, Swetha Ramadesikan, Donna Fekete, Ruben Claudio Aguilar
Lowe syndrome is an X-linked condition characterized by congenital cataracts, neurological abnormalities and kidney malfunction. This lethal disease is caused by mutations in the OCRL1 gene, which encodes for the phosphatidylinositol 5-phosphatase Ocrl1. While in the past decade we witnessed substantial progress in the identification and characterization of LS patient cellular phenotypes, many of these studies have been performed in knocked-down cell lines or patient's cells from accessible cell types such as skin fibroblasts, and not from the organs affected...
2018: PloS One
https://www.readbyqxmd.com/read/29443553/highly-conserved-motifs-within-the-large-sec7-arf-guanine-nucleotide-exchange-factor-gbf1-target-it-to-the-golgi-and-are-critical-for-gbf1-activity
#10
Cristian A Pocognoni, Ekaterina G Viktorova, John Wright, Justyna M Meissner, Garrett Sager, Eunjoo Lee, George A Belov, Elizabeth Sztul
Cellular life requires the activation of the ADP-ribosylation factors (ARFs) by GBF1, a guanine nucleotide exchange factor (GEF) with a highly conserved catalytic Sec7 domain (Sec7d). In addition to the Sec7d, GBF1 contains other conserved domains whose functions remain unclear. Here, we focus on HDS2 (homology downstream of the Sec7d 2) domain because the L1246R substitution within the HDS2 α-helix 5 of the zebrafish GBF1 ortholog causes vascular hemorrhaging and embryonic lethality (13). To dissect the structure/function relationships within HDS2, we generated six variants, in which the most conserved residues within α-helices 1, 2, 4 and 6 were mutated to alanines...
February 14, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29441061/profiling-of-human-molecular-pathways-affected-by-retrotransposons-at-the-level-of-regulation-by-transcription-factor-proteins
#11
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29440677/nanobody-triggered-lockdown-of-vsrs-reveals-ligand-reloading-in-the-golgi
#12
Simone Früholz, Florian Fäßler, Üner Kolukisaoglu, Peter Pimpl
Protein degradation in lytic compartments is crucial for eukaryotic cells. At the heart of this process, vacuolar sorting receptors (VSRs) bind soluble hydrolases in the secretory pathway and release them into the vacuolar route. Sorting efficiency is suggested to result from receptor recycling. However, how and to where plant VSRs recycle remains controversial. Here we present a nanobody-epitope interaction-based protein labeling and tracking approach to dissect their anterograde and retrograde transport routes in vivo...
February 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29440562/myb52-negatively-regulates-pectin-demethylesterification-in-seed-coat-mucilage
#13
Dachuan Shi, Angyan Ren, Xianfeng Tang, Guang Qi, Zongchang Xu, Guohua Chai, Ruibo Hu, Gongke Zhou, Yingzhen Kong
Pectins are synthesized and methyl-esterified in the Golgi apparatus and then demethylesterified by pectin methylesterases (PMEs) located in the cell wall. The degree of methylesterification affects the functional properties of pectin, and thereby influences plant growth and development, as well as defense responses. However, little is known about the mechanisms that regulate pectin demethylesterification. Here, we show that in seed coat mucilage the absence of the MYB52 transcription factor is correlated with an increase in PME activity and a decrease in the degree of pectin methylesterification...
February 9, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29437695/snx18-regulates-atg9a-trafficking-from-recycling-endosomes-by-recruiting-dynamin-2
#14
Kristiane Søreng, Michael J Munson, Christopher A Lamb, Gunnveig T Bjørndal, Serhiy Pankiv, Sven R Carlsson, Sharon A Tooze, Anne Simonsen
Trafficking of mammalian ATG9A between the Golgi apparatus, endosomes and peripheral ATG9A compartments is important for autophagosome biogenesis. Here, we show that the membrane remodelling protein SNX18, previously identified as a positive regulator of autophagy, regulates ATG9A trafficking from recycling endosomes. ATG9A is recruited to SNX18-induced tubules generated from recycling endosomes and accumulates in juxtanuclear recycling endosomes in cells lacking SNX18. Binding of SNX18 to Dynamin-2 is important for ATG9A trafficking from recycling endosomes and for formation of ATG16L1- and WIPI2-positive autophagosome precursor membranes...
February 7, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29437275/intersection-of-endocytic-and-exocytic-systems-in-toxoplasma-gondii
#15
Olivia L McGovern, Yolanda Rivera-Cuevas, Geetha Kannan, Andrew Narwold, Vern B Carruthers
Host cytosolic proteins are endocytosed by Toxoplasma gondii and degraded in its lysosome-like compartment, the VAC, but the dynamics and route of endocytic trafficking remain undefined. Conserved endocytic components and plant-like features suggest T. gondii endocytic trafficking involves transit through early and late endosome-like compartments (ELCs) and potentially the trans-Golgi network (TGN) as in plants. However, exocytic trafficking to regulated secretory organelles, micronemes and rhoptries, also proceeds through ELCs and requires classical endocytic components including a dynamin-related protein, DrpB...
February 13, 2018: Traffic
https://www.readbyqxmd.com/read/29431830/sensors-for-measuring-subcellular-zinc-pools
#16
REVIEW
Pauline Chabosseau, Jason Woodier, Rebecca Cheung, Guy A Rutter
Zinc homeostasis is essential for normal cellular function, and defects in this process are associated with a number of diseases including type 2 diabetes (T2D), neurological disorders and cardiovascular disease. Thus, variants in the SLC30A8 gene, encoding the vesicular/granular zinc transporter ZnT8, are associated with altered insulin release and increased T2D risk while the zinc importer ZIP12 is implicated in pulmonary hypertension. In light of these, and findings in other diseases, recent efforts have focused on the development of refined sensors for intracellular free zinc ions that can be targeted to subcellular regions including the cytosol, endoplasmic reticulum (ER), secretory granules, Golgi apparatus, nucleus and the mitochondria...
February 12, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29428502/protein-4-1n-is-required-for-the-formation-of-the-lateral-membrane-domain-in-human-bronchial-epithelial-cells
#17
Yaomei Wang, Huizhen Zhang, Qiaozhen Kang, Jing Liu, Haibo Weng, Wei Li, Narla Mohandas, Xiuli An, Lixiang Chen
The membrane skeleton forms a scaffold on the cytoplasmic side of the plasma membrane. The erythrocyte membrane represents an archetype of such structural organization. It has been documented that a similar membrane skeleton also exits in the Golgi complex. It has been previously shown that βII spectrin and ankyrin G are localized at the lateral membrane of human bronchial epithelial cells. Here we show that protein 4.1N is also located at the lateral membrane where it associates E-cadherin, β-catenin and βII spectrin...
February 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29426932/quantitative-analysis-of-receptor-mediated-uptake-and-pro-apoptotic-activity-of-mistletoe-lectin-1-by-high-content-imaging
#18
N Beztsinna, M B C de Matos, J Walther, C Heyder, E Hildebrandt, G Leneweit, E Mastrobattista, R J Kok
Ribosome inactivating proteins (RIPs) are highly potent cytotoxins that have potential as anticancer therapeutics. Mistletoe lectin 1 (ML1) is a heterodimeric cytotoxic protein isolated from European Mistletoe and belongs to RIP class II. The aim of this project was to systematically study ML1 cell binding, endocytosis pathway(s), subcellular processing and apoptosis activation. For this purpose, state of the art cell imaging equipment and automated image analysis algorithms were used. ML1 displayed very fast binding to sugar residues on the membrane and energy-dependent uptake in CT26 cells...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29426865/the-wdr11-complex-facilitates-the-tethering-of-ap-1-derived-vesicles
#19
Paloma Navarro Negredo, James R Edgar, Paul T Manna, Robin Antrobus, Margaret S Robinson
Vesicluar transport of proteins from endosomes to the trans-Golgi network (TGN) is an essential cellular pathway, but much of its machinery is still unknown. A screen for genes involved in endosome-to-TGN trafficking produced two hits, the adaptor protein-1 (AP-1 complex), which facilitates vesicle budding, and WDR11. Here we demonstrate that WDR11 forms a stable complex with two other proteins, which localises to the TGN region and does not appear to be associated with AP-1, suggesting it may act downstream from budding...
February 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29425772/ultrastructure-and-function-of-the-seminal-vesicle-of-bittacidae-insecta-mecoptera
#20
Qi-Hui Lyu, Bei-Bei Zhang, Bao-Zhen Hua
The fine structure of the seminal vesicle and reproductive accessory glands was investigated in Bittacidae of Mecoptera using light and transmission electron microscopy. The male reproductive system of Bittacidae mainly consists of a pair of testes, a pair of vasa deferentia, and an ejaculatory sac. The vas deferens is greatly expanded for its middle and medio-posterior parts to form a well-developed seminal vesicle. The seminal vesicle is composed of layers of developed muscles and a mono-layered epithelium surrounding the small central lumen...
February 6, 2018: Arthropod Structure & Development
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