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https://www.readbyqxmd.com/read/27911384/analysis-of-scap-n-glycosylation-and-trafficking-in-human-cells
#1
Chunming Cheng, Jeffrey Yunhua Guo, Feng Geng, Xiaoning Wu, Xiang Cheng, Qiyue Li, Deliang Guo
Elevated lipogenesis is a common characteristic of cancer and metabolic diseases. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors controlling the expression of genes important for the synthesis of cholesterol, fatty acids and phospholipids, are frequently upregulated in these diseases. In the process of SREBP nuclear translocation, SREBP-cleavage activating protein (SCAP) plays a central role in the trafficking of SREBP from the endoplasmic reticulum (ER) to the Golgi and in subsequent proteolysis activation...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27905160/improving-the-solubility-of-artificial-ligands-of-streptavidin-to-enable-more-practical-reversible-switching-of-protein-localization-in-cells
#2
Ryo Tachibana, Takuya Terai, Gaelle Boncompain, Shigeru Sugiyama, Nae Saito, Franck Perez, Yasuteru Urano
Chemical inducers that can control target protein localization in living cells are powerful tools to investigate dynamic biological systems. We recently reported the "retention using selective hook" (RUSH) system for reversible localization change of proteins of interest by addition/washout of small molecules called artificial ligands of streptavidin (ALiS). However, the utility of previously developed ALiS is restricted by limited solubility in water. Here, we overcome this problem by X-ray crystal structure-guided design of a more soluble ALiS derivative (ALiS-3), which retains sufficient streptavidin-binding affinity for use in the RUSH system...
November 30, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27904578/low-energy-density-diet-weight-loss-maintenance-and-risk-of-cardiovascular-disease-following-a-recent-weight-reduction-program-a-randomized-control-trial
#3
Golgis Karimi, Leila Azadbakht, Fahimeh Haghighatdoost, Ahmad Esmaillzadeh
BACKGROUND: Little is known about the effects of a low energy dense diet on weight maintenance and cardiovascular risks following a recent weight reduction. Therefore, we assessed if weight maintenance, lipid profiles, and glycemic control differ between low energy density (LED) diet and usual diet consumers following a recent weight reduction. MATERIALS AND METHODS: In this randomized controlled clinical trial study in a parallel design, we recruited 70 patients with the history of weight reduction in the recent 1 year...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27903609/protein-sorting-at-the-er-golgi-interface
#4
REVIEW
Natalia Gomez-Navarro, Elizabeth Miller
Protein traffic is of critical importance for normal cellular physiology. In eukaryotes, spherical transport vesicles move proteins and lipids from one internal membrane-bound compartment to another within the secretory pathway. The process of directing each individual protein to a specific destination (known as protein sorting) is a crucial event that is intrinsically linked to vesicle biogenesis. In this review, we summarize the principles of cargo sorting by the vesicle traffic machinery and consider the diverse mechanisms by which cargo proteins are selected and captured into different transport vesicles...
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27901063/regulation-of-%C3%AE-2b-adrenergic-receptor-cell-surface-transport-by-gga1-and-gga2
#5
Maoxiang Zhang, Wei Huang, Jie Gao, Alvin V Terry, Guangyu Wu
The molecular mechanisms that control the targeting of newly synthesized G protein-coupled receptors (GPCRs) to the functional destinations remain poorly elucidated. Here, we have determined the role of Golgi-localized, γ-adaptin ear domain homology, ADP ribosylation factor-binding proteins 1 and 2 (GGA1 and GGA2) in the cell surface transport of α2B-adrenergic receptor (α2B-AR), a prototypic GPCR, and studied the underlying mechanisms. We demonstrated that knockdown of GGA1 and GGA2 by shRNA and siRNA significantly reduced the cell surface expression of inducibly expressed α2B-AR and arrested the receptor in the perinuclear region...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901058/a-kinase-anchoring-protein-4-akap4-is-an-erk1-2-substrate-and-a-switch-molecule-between-camp-pka-and-pkc-erk1-2-in-human-spermatozoa
#6
Liat Rahamim Ben-Navi, Tal Almog, Zhong Yao, Rony Seger, Zvi Naor
Mammalian spermatozoa undergo capacitation and acrosome reaction in order to fertilize the egg. The PKC-ERK1/2 pathway plays an important role in human spermatozoa motility, capacitation and the acrosome reaction. Here we demonstrate that ERK1/2 phosphorylates proAKAP4 on Thr265 in human spermatozoa in vitro and in vivo. Cyclic AMP (cAMP) had no effect on ERK1/2 activity in human spermatozoa, but stimulated the MAPK in mouse pituitary LβT2 gonadotrope cells. cAMP via PKA attenuates PKC-dependent ERK1/2 activation only in the presence of proAKAP4...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899443/rab43-facilitates-cross-presentation-of-cell-associated-antigens-by-cd8%C3%AE-dendritic-cells
#7
Nicole M Kretzer, Derek J Theisen, Roxane Tussiwand, Carlos G Briseño, Gary E Grajales-Reyes, Xiaodi Wu, Vivek Durai, Jörn Albring, Prachi Bagadia, Theresa L Murphy, Kenneth M Murphy
In this study, to examine cross-presentation by classical dendritic cells (DCs; cDCs), we evaluated the role of RAB43, a protein found to be selectively expressed by Batf3-dependent CD8α(+) and CD103(+) compared with other DC subsets and immune lineages. Using a specific monoclonal antibody, we localized RAB43 expression to the Golgi apparatus and LAMP1(-) cytoplasmic vesicles. Mice with germline or conditional deletion of Rab43 are viable and fertile and have normal development of cDCs but show a defect for in vivo and in vitro cross-presentation of cell-associated antigen...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27895752/expression-of-golph3-protein-in-colon-cancer-tissues-and-its-association-with-the-prognosis-of-patients
#8
Bo Zhou, Gongping Wang, Shegan Gao, Ye Chen, Canhui Jin, Zengfang Wang, Yantong Yang, Zhikun Ma, Wei Zhang, Xiaoshan Feng
The present study aimed to investigate the expression of Golgi phosphoprotein-3 (GOLPH3) protein in colon cancer tissues and the association with the prognosis of patients. In total, 98 patients with colon cancer admitted to The First Affiliated Hospital of Henan University of Science and Technology for surgery between June 2011 and June 2013 were taken as the observation group. In addition, 15 healthy individuals, determined by enteroscopy, were taken as the control group. The expressions of GOLPH3 mRNA and protein were detected by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895225/loss-of-inositol-phosphorylceramide-sphingolipid-mannosylation-induces-plant-immune-responses-and-reduces-cellulose-content-in-arabidopsis
#9
Lin Fang, Toshiki Ishikawa, Emilie A Rennie, Gosia M Murawska, Jeemeng Lao, Jingwei Yan, Alex Yl Tsai, Edward E K Baidoo, Jun Xu, Jay D Keasling, Taku Demura, Maki Kawai-Yamada, Henrik Vibe Scheller, Jenny C Mortimer
Glycosylinositol phosphorylceramides (GIPCs) are a class of glycosylated sphingolipids found in plants, fungi, and protozoa. These lipids are abundant in the plant plasma membrane, forming ~25% of total plasma membrane lipids. Little is known about the function of the glycosylated headgroup, but two recent studies have indicated that they play a key role in plant signaling and defense. Here, we show that a member of glycosyltransferase (GT) family 64, previously named ECTOPICALLY PARTING CELLS1 (EPC1), is likely a Golgi-localized GIPC-specific mannosyl-transferase, which we renamed GIPC MANNOSYL-TRANSFERASE1 (GMT1)...
November 28, 2016: Plant Cell
https://www.readbyqxmd.com/read/27895204/two-h-type-thioredoxins-interact-with-the-pho2ubiquitin-conjugating-e2-enzyme-to-fine-tune-phosphate-homeostasis
#10
Yinghui Ying, Wenhao Yue, Shoudong Wang, Shuai Li, Min Wang, Yang Zhao, Chuang Wang, Chuanzao Mao, James Whelan, Huixia Shou
Phosphate over-accumulator 2 (PHO2) encodes an ubiquitin-conjugating E2 enzyme that is a major negative regulator of the inorganic phosphate (Pi)-starvation response-signaling pathway. A yeast-two-hybrid (Y2H) screen in Oryza sativa (Os, rice) using OsPHO2 as bait, revealed an interaction between OsPHO2 and two h-type thioredoxins, OsTrxh1 and OsTrxh4. These interactions were confirmed in vivo using bimolecular fluorescence complementation (BiFC) of OsPHO2 and OsTrxh1/h4 in rice protoplasts, and by in vitro pull-down assays with 6His-tagged OsTrxh1/h4 and GST-tagged OsPHO2...
November 28, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27894594/alterations-of-golgi-organization-in-alzheimer-s-disease-a-cause-or-a-consequence
#11
REVIEW
Inmaculada Ayala, Antonino Colanzi
The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized in polarized manner, which are interconnected by membrane tubules to constitute the Golgi ribbon, located in the proximity of the centrosome. Besides the processing and transport of cargo, the Golgi complex is actively involved in the regulation of mitotic entry, cytoskeleton organization and dynamics, calcium homeostasis, and apoptosis, representing a signalling platform for the control of several cellular functions, including signalling initiated by receptors located at the plasma membrane...
November 19, 2016: Tissue & Cell
https://www.readbyqxmd.com/read/27894086/the-anti-tumor-drug-2-hydroxyoleic-acid-minerval-stimulates-signaling-and-retrograde-transport
#12
Maria L Torgersen, Tove Irene Klokk, Simona Kavaliauskiene, Christian Klose, Kai Simons, Tore Skotland, Kirsten Sandvig
2-hydroxyoleic acid (OHOA, Minerval®) is an example of a substance used for membrane lipid therapy, where the cellular membranes rather than specific proteins constitute the therapeutical target. OHOA is thought to mediate its anti-tumor effect by affecting the biophysical properties of membranes, which leads to altered recruitment and activation of amphitropic proteins, altered cellular signaling, and eventual cell death. Little is known about the initial signaling events upon treatment with OHOA, and whether the altered membrane properties would have any impact on the dynamic intracellular transport system...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893466/cd30-expression-is-rare-in-myeloid-leukemia-cutis-a-study-of-55-cases-and-implications-for-routine-diagnostic-algorithms
#13
Olakunle Ogunrinade, David Terrano, April Chiu, Melissa Pulitzer
Expression of CD30 in blastoid cutaneous infiltrates typically signifies a CD30 lymphoproliferative disorder, often requiring minimal immunohistochemical workup, if clinically consonant. However, myeloid and other hematologic malignancies often express CD30. We retrospectively examined the prevalence of CD30 expression in 41 patients (median age 59) and 55 biopsies with the diagnosis of leukemia cutis (LC) to determine whether an extensive immunohistochemical workup is warranted in all large, round cell CD30 cutaneous infiltrates...
November 22, 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27889386/protein-disulfide-isomerases-redox-connections-in-and-out-of-the-endoplasmic-reticulum
#14
Ana Iochabel Soares Moretti, Francisco Rafael Martins Laurindo
Protein disulfide isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily. As redox folding catalysts from the endoplasmic reticulum (ER), their roles in ER-related redox homeostasis and signaling is well-studied. PDIA1 exerts thiol oxidation/reduction and isomerization, plus chaperone effects. Also, substantial evidence indicates that PDIs regulate thiol-disulfide switches in other cell locations such as cell surface and possibly cytosol. Subcellular PDI translocation routes remain unclear and seem Golgi-independent...
November 23, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27889239/structural-mechanism-for-cargo-recognition-by-the-retromer-complex
#15
María Lucas, David C Gershlick, Ander Vidaurrazaga, Adriana L Rojas, Juan S Bonifacino, Aitor Hierro
Retromer is a multi-protein complex that recycles transmembrane cargo from endosomes to the trans-Golgi network and the plasma membrane. Defects in retromer impair various cellular processes and underlie some forms of Alzheimer's disease and Parkinson's disease. Although retromer was discovered over 15 years ago, the mechanisms for cargo recognition and recruitment to endosomes have remained elusive. Here, we present an X-ray crystallographic analysis of a four-component complex comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin SNX3, and a recycling signal from the divalent cation transporter DMT1-II...
November 22, 2016: Cell
https://www.readbyqxmd.com/read/27888615/unconjugated-secondary-bile-acids-activate-the-unfolded-protein-response-and-induce-golgi-fragmentation-via-a-src-kinase-dependant-mechanism
#16
Ruchika Sharma, Francis Quilty, John F Gilmer, Aideen Long, Anne-Marie Byrne
Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888070/phosphoramide-mustard-induces-autophagy-markers-and-mtor-inhibition-prevents-follicle-loss-due-to-phosphoramide-mustard-exposure
#17
Jill A Madden, Porsha Q Thomas, Aileen F Keating
Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide. Postnatal day 4 Fisher 344 rat ovaries were exposed to vehicle control (1% DMSO) or PM (60μM) ± LY294002 or rapamycin for 2 or 4 d. Transmission election microscopy revealed abnormally large golgi apparatus and electron dense mitochondria in PM-exposed ovaries prior to and at the time of follicle depletion. PM exposure increased (P<0.05) mRNA abundance of Bbc3, Cdkn1a, Ctfr, Edn1, Gstp1, Nqo1, Tlr4, Tnfrsfla, Txnrd1 and decreased (P<0...
November 22, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27883263/cargo-selectivity-of-yeast-sorting-nexins
#18
Björn D M Bean, Michael Davey, Elizabeth Conibear
Sorting nexins are PX domain-containing proteins that bind phospholipids and often act in membrane trafficking where they help to select cargo. However, the functions and cargo specificities of many sorting nexins are unknown. Here, a high-throughput imaging screen was used to identify new sorting nexin cargo in the yeast Saccharomyces cerevisiae. Deletions of nine different sorting nexins were screened for mislocalization of a set of GFP-tagged membrane proteins found at the plasma membrane, Golgi or endosomes...
November 24, 2016: Traffic
https://www.readbyqxmd.com/read/27882938/neutral-sphingomyelinase-smpd3-deficiency-disrupts-the-golgi-secretory-pathway-and-causes-growth-inhibition
#19
Wilhelm Stoffel, Ina Hammels, Bitta Jenke, Erika Binczek, Inga Schmidt-Soltau, Susanne Brodesser, Astrid Schauss, Julia Etich, Juliane Heilig, Frank Zaucke
Systemic loss of neutral sphingomyelinase (SMPD3) in mice leads to a novel form of systemic, juvenile hypoplasia (dwarfism). SMPD3 deficiency in mainly two growth regulating cell types contributes to the phenotype, in chondrocytes of skeletal growth zones to skeletal malformation and chondrodysplasia, and in hypothalamic neurosecretory neurons to systemic hypothalamus-pituitary-somatotropic hypoplasia. The unbiased smpd3-/- mouse mutant and derived smpd3-/- primary chondrocytes were instrumental in defining the enigmatic role underlying the systemic and cell autonomous role of SMPD3 in the Golgi compartment...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27882921/a-mutation-in-vps15-pik3r4-causes-a-ciliopathy-and-affects-ift20-release-from-the-cis-golgi
#20
Corinne Stoetzel, Séverine Bär, Johan-Owen De Craene, Sophie Scheidecker, Christelle Etard, Johana Chicher, Jennifer R Reck, Isabelle Perrault, Véronique Geoffroy, Kirsley Chennen, Uwe Strähle, Philippe Hammann, Sylvie Friant, Hélène Dollfus
Ciliopathies are a group of diseases that affect kidney and retina among other organs. Here, we identify a missense mutation in PIK3R4 (phosphoinositide 3-kinase regulatory subunit 4, named VPS15) in a family with a ciliopathy phenotype. Besides being required for trafficking and autophagy, we show that VPS15 regulates primary cilium length in human fibroblasts, as well as ciliary processes in zebrafish. Furthermore, we demonstrate its interaction with the golgin GM130 and its localization to the Golgi. The VPS15-R998Q patient mutation impairs Golgi trafficking functions in humanized yeast cells...
November 24, 2016: Nature Communications
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