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https://www.readbyqxmd.com/read/28924031/cytoplasmic-copper-detoxification-in-salmonella-can-contribute-to-sodc-metalation-but-is-dispensable-during-systemic-infection
#1
Luke A Fenlon, James M Slauch
Salmonella Typhimurium is a leading cause of foodborne disease worldwide. Severe infections result from the ability of S. Typhimurium to survive within host immune cells, despite being exposed to various host antimicrobial factors. SodCI, a copper-zinc cofactored superoxide dismutase, is required to defend against phagocytic superoxide. SodCII, an additional periplasmic superoxide dismutase, although produced during infection, does not function in the host. Previous studies suggested that CueP, a periplasmic copper binding protein, facilitates acquisition of copper by SodCII...
September 18, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28923515/integrative-functions-of-the-mitochondrial-contact-site-and-cristae-organizing-system
#2
REVIEW
Stefan Schorr, Martin van der Laan
Mitochondria are complex double-membrane-bound organelles of eukaryotic cells that function as energy-converting powerhouses, metabolic factories and signaling centers. The outer membrane controls the exchange of material and information with other cellular compartments. The inner membrane provides an extended, highly folded surface for selective transport and energy-coupling reactions. It can be divided into an inner boundary membrane and tubular or lamellar cristae membranes that accommodate the oxidative phosphorylation units...
September 15, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28923514/cell-polarity-and-planar-cell-polarity-pcp-in-spermatogenesis
#3
REVIEW
Haiqi Chen, Dolores D Mruk, Wing-Yee Lui, Chris K C Wong, Will M Lee, C Yan Cheng
In adult mammalian testes, spermatids, most notably step 17-19 spermatids in stage IV-VIII tubules, are aligned with their heads pointing toward the basement membrane and their tails toward the tubule lumen. On the other hand, these polarized spermatids also align across the plane of seminiferous epithelium, mimicking planar cell polarity (PCP) found in other hair cells in cochlea (inner ear). This orderly alignment of developing spermatids during spermiogenesis is important to support spermatogenesis, such that the maximal number of developing spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes...
September 15, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28916471/the-pyk2-mcu-pathway-in-the-rat-middle-cerebral-artery-occlusion-model-of-ischemic-stroke
#4
Kun Zhang, Jiajia Yan, Liang Wang, Xinying Tian, Tong Zhang, Li Guo, Bin Li, Wang Wang, Xiaoyun Liu
Mitochondrial dysfunction caused by Ca(2+) overload plays an important role in ischemia-induced brain damage. Mitochondrial calcium uniporter (MCU), located on the mitochondrial inner membrane, is the major channel responsible for mitochondrial Ca(2+) uptake. Activated proline-rich tyrosine kinase 2 (Pyk2) can directly phosphorylate MCU, which enhances mitochondrial Ca(2+) uptake in cardiomyocytes. It has been suggested that the Pyk2/MCU pathway may be a novel therapeutic target in stress-induced cellular apoptosis...
September 12, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28915323/hair-cell-transduction-tuning-and-synaptic-transmission-in-the-mammalian-cochlea
#5
Robert Fettiplace
Sound pressure fluctuations striking the ear are conveyed to the cochlea, where they vibrate the basilar membrane on which sit hair cells, the mechanoreceptors of the inner ear. Recordings of hair cell electrical responses have shown that they transduce sound via submicrometer deflections of their hair bundles, which are arrays of interconnected stereocilia containing the mechanoelectrical transducer (MET) channels. MET channels are activated by tension in extracellular tip links bridging adjacent stereocilia, and they can respond within microseconds to nanometer displacements of the bundle, facilitated by multiple processes of Ca2+-dependent adaptation...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28913898/structural-basis-for-binding-and-transfer-of-heme-in-bacterial-heme-acquisition-systems
#6
Youichi Naoe, Nozomi Nakamura, Md Mahfuzur Rahman, Takehiko Tosha, Satoru Nagatoishi, Kouhei Tsumoto, Yoshitsugu Shiro, Hiroshi Sugimoto
Periplasmic heme-binding proteins (PBPs) in Gram-negative bacteria are components of the heme acquisition system. These proteins shuttle heme across the periplasmic space from outer membrane receptors to ATP-binding cassette (ABC) heme importers located in the inner-membrane. In the present study, we characterized the structures of PBPs found in the pathogen Burkholderia cenocepacia (BhuT) and in the thermophile Roseiflexus sp. RS-1 (RhuT) in the heme-free and heme-bound forms. The conserved motif, in which a well-conserved Tyr interacts with the nearby Arg coordinates on heme iron, was observed in both PBPs...
September 14, 2017: Proteins
https://www.readbyqxmd.com/read/28911913/phosphatidic-acid-and-cardiolipin-coordinate-mitochondrial-dynamics
#7
REVIEW
Shoichiro Kameoka, Yoshihiro Adachi, Koji Okamoto, Miho Iijima, Hiromi Sesaki
Membrane organelles comprise both proteins and lipids. Remodeling of these membrane structures is controlled by interactions between specific proteins and lipids. Mitochondrial structure and function depend on regulated fusion and the division of both the outer and inner membranes. Here we discuss recent advances in the regulation of mitochondrial dynamics by two critical phospholipids, phosphatidic acid (PA) and cardiolipin (CL). These two lipids interact with the core components of mitochondrial fusion and division (Opa1, mitofusin, and Drp1) to activate and inhibit these dynamin-related GTPases...
September 11, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28904209/drosophila-mic60-mitofilin-conducts-dual-roles-in-mitochondrial-motility-and-crista-structure
#8
Pei-I Tsai, Amanda M Papakyrikos, Chung-Han Hsieh, Xinnan Wang
MIC60/mitofilin constitutes a hetero-oligomeric complex on the inner mitochondrial membranes to maintain crista structure. However, little is known about its physiological functions. Here, by characterizing Drosophila MIC60 mutants, we define its roles in vivo We discover that MIC60 performs dual functions to maintain mitochondrial homeostasis. In addition to its canonical role in crista membrane structure, MIC60 regulates mitochondrial motility, likely by influencing protein levels of the outer mitochondrial membrane protein Miro that anchors mitochondria to the microtubule motors...
September 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28904017/eliciting-improved-antibacterial-efficacy-of-host-proteins-in-the-presence-of-antibiotics
#9
Joanna Jammal, Fadia Zaknoon, Amram Mor
We recently reported the aptitude of a membrane-active lipopeptide (C10OOc12O) to sensitize gram-negative bacilli (GNB) to host antibacterial proteins. Here we explored the potential of harnessing such capacity in the presence of antibiotics. For this purpose, we compared Escherichia coli sensitization to antibiotics in broth and plasma; assessed inner and outer membrane damages using scanning electron microscopy, dyes, and mutant strains; and assessed the ability to affect disease course using the mouse peritonitis-sepsis model for mono- and combination therapies...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28903457/the-lifecycle-of-the-ebola-virus-in-host-cells
#10
REVIEW
Dong-Shan Yu, Tian-Hao Weng, Xiao-Xin Wu, Frederick X C Wang, Xiang-Yun Lu, Hai-Bo Wu, Nan-Ping Wu, Lan-Juan Li, Hang-Ping Yao
Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family Filoviridae. However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. This review describes the biological functions of EBOV proteins and their roles in the lifecycle, summarizes the factors related to EBOV proteins or RNA expression throughout the different phases, and reviews advances with regards to the molecular events and mechanisms of the EBOV lifecycle...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903085/multiscale-molecular-dynamics-simulations-of-lipid-interactions-with-p-glycoprotein-in-a-complex-membrane
#11
Laura Domicevica, Heidi Koldsø, Philip C Biggin
P-glycoprotein (P-gp) can transport a wide range of very different hydrophobic organic molecules across the membrane. Its ability to extrude molecules from the cell creates delivery problems for drugs that target proteins in the central nervous system (CNS) and also causes drug-resistance in many forms of cancer. Whether a drug will be susceptible to export by P-gp is difficult to predict and currently this is usually assessed with empirical and/or animal models. Thus, there is a need to better understand how P-gp works at the molecular level in order to fulfil the 3Rs: Refinement, reduction and replacement of animals in research...
September 2, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28900026/activity-related-conformational-changes-in-d-d-carboxypeptidases-revealed-by-in-vivo-periplasmic-f%C3%A3-rster-resonance-energy-transfer-assay-in-escherichia-coli
#12
Nils Y Meiresonne, René van der Ploeg, Mark A Hink, Tanneke den Blaauwen
One of the mechanisms of β-lactam antibiotic resistance requires the activity of d,d-carboxypeptidases (d,d-CPases) involved in peptidoglycan (PG) synthesis, making them putative targets for new antibiotic development. The activity of PG-synthesizing enzymes is often correlated with their association with other proteins. The PG layer is maintained in the periplasm between the two membranes of the Gram-negative cell envelope. Because no methods existed to detect in vivo interactions in this compartment, we have developed and validated a Förster resonance energy transfer assay...
September 12, 2017: MBio
https://www.readbyqxmd.com/read/28900025/psp-stress-response-proteins-form-a-complex-with-mislocalized-secretins-in-the-yersinia-enterocolitica-cytoplasmic-membrane
#13
Disha Srivastava, Amal Moumene, Josué Flores-Kim, Andrew J Darwin
The bacterial phage shock protein system (Psp) is a conserved extracytoplasmic stress response that is essential for the virulence of some pathogens, including Yersinia enterocolitica It is induced by events that can compromise inner membrane (IM) integrity, including the mislocalization of outer membrane pore-forming proteins called secretins. In the absence of the Psp system, secretin mislocalization permeabilizes the IM and causes rapid cell death. The Psp proteins PspB and PspC form an integral IM complex with two independent roles...
September 12, 2017: MBio
https://www.readbyqxmd.com/read/28893864/the-beach-protein-lrba-is-required-for-hair-bundle-maintenance-in-cochlear-hair-cells-and-for-hearing
#14
Christian Vogl, Tanvi Butola, Natja Haag, Torben J Hausrat, Michael G Leitner, Michel Moutschen, Philippe P Lefèbvre, Carsten Speckmann, Lillian Garrett, Lore Becker, Helmut Fuchs, Martin Hrabe de Angelis, Sandor Nietzsche, Michael M Kessels, Dominik Oliver, Matthias Kneussel, Manfred W Kilimann, Nicola Strenzke
Lipopolysaccharide-responsive beige-like anchor protein (LRBA) belongs to the enigmatic class of BEACH domain-containing proteins, which have been attributed various cellular functions, typically involving intracellular protein and membrane transport processes. Here, we show that LRBA deficiency in mice leads to progressive sensorineural hearing loss. In LRBA knockout mice, inner and outer hair cell stereociliary bundles initially develop normally, but then partially degenerate during the second postnatal week...
September 11, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28882140/role-of-mitochondrial-dysfunction-and-dysregulation-of-ca-2-homeostasis-in-the-pathophysiology-of-insulin-resistance-and-type-2-diabetes
#15
REVIEW
Chih-Hao Wang, Yau-Huei Wei
Metabolic diseases such as obesity, type 2 diabetes (T2D) and insulin resistance have attracted great attention from biomedical researchers and clinicians because of the astonishing increase in its prevalence. Decrease in the capacity of oxidative metabolism and mitochondrial dysfunction are a major contributor to the development of these metabolic disorders. Recent studies indicate that alteration of intracellular Ca(2+) levels and downstream Ca(2+)-dependent signaling pathways appear to modulate gene transcription and the activities of many enzymes involved in cellular metabolism...
September 7, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28881650/apex2-enhanced-electron-microscopy-distinguishes-sigma-1-receptor-localization-in-the-nucleoplasmic-reticulum
#16
Timur A Mavlyutov, Huan Yang, Miles L Epstein, Arnold E Ruoho, Jay Yang, Lian-Wang Guo
The sigma-1 receptor (Sig1R) is an endoplasmic reticulum chaperonin that is attracting tremendous interest as a potential anti-neurodegenerative target. While this membrane protein is known to reside in the inner nuclear envelope (NE) and influences transcription, apparent Sig1R presence in the nucleoplasm is often observed, seemingly contradicting its NE localization. We addressed this confounding issue by applying an antibody-free approach of electron microscopy (EM) to define Sig1R nuclear localization. We expressed APEX2 peroxidase fused to Sig1R-GFP in a Sig1R-null NSC34 neuronal cell line generated with CRISPR-Cas9...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879181/regulation-of-the-sar1-gtpase-cycle-is-necessary-for-large-cargo-secretion-from-the-endoplasmic-reticulum
#17
REVIEW
Kota Saito, Miharu Maeda, Toshiaki Katada
Proteins synthesized within the endoplasmic reticulum (ER) are transported to the Golgi via coat protein complex II (COPII)-coated vesicles. The formation of COPII-coated vesicles is regulated by the GTPase cycle of Sar1. Activated Sar1 is recruited to ER membranes and forms a pre-budding complex with cargoes and the inner-coat complex. The outer-coat complex then stimulates Sar1 inactivation and completes vesicle formation. The mechanisms of forming transport carriers are well-conserved among species; however, in mammalian cells, several cargo molecules such as collagen, and chylomicrons are too large to be accommodated in conventional COPII-coated vesicles...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28878347/targeting-bacterial-cardiolipin-enriched-microdomains-an-antimicrobial-strategy-used-by-amphiphilic-aminoglycoside-antibiotics
#18
Micheline El Khoury, Jitendriya Swain, Guillaume Sautrey, Louis Zimmermann, Patrick Van Der Smissen, Jean-Luc Décout, Marie-Paule Mingeot-Leclercq
Some bacterial proteins involved in cell division and oxidative phosphorylation are tightly bound to cardiolipin. Cardiolipin is a non-bilayer anionic phospholipid found in bacterial inner membrane. It forms lipid microdomains located at the cell poles and division plane. Mechanisms by which microdomains are affected by membrane-acting antibiotics and the impact of these alterations on membrane properties and protein functions remain unclear. In this study, we demonstrated cardiolipin relocation and clustering as a result of exposure to a cardiolipin-acting amphiphilic aminoglycoside antibiotic, the 3',6-dinonyl neamine...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871245/comparative-genomic-analysis-of-neutrophilic-iron-ii-oxidizer-genomes-for-candidate-genes-in-extracellular-electron-transfer
#19
Shaomei He, Roman A Barco, David Emerson, Eric E Roden
Extracellular electron transfer (EET) is recognized as a key biochemical process in circumneutral pH Fe(II)-oxidizing bacteria (FeOB). In this study, we searched for candidate EET genes in 73 neutrophilic FeOB genomes, among which 43 genomes are complete or close-to-complete and the rest have estimated genome completeness ranging from 5 to 91%. These neutrophilic FeOB span members of the microaerophilic, anaerobic phototrophic, and anaerobic nitrate-reducing FeOB groups. We found that many microaerophilic and several anaerobic FeOB possess homologs of Cyc2, an outer membrane cytochrome c originally identified in Acidithiobacillus ferrooxidans...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28870843/phosphatidylserine-a-cancer-cell-targeting-biomarker
#20
REVIEW
Bhupender Sharma, Shamsher S Kanwar
Cancer is a leading cause of mortality and morbidity globally. Many prominent cancer-associated molecules have been identified over the recent years which include EGFR, CD44, TGFbRII, HER2, miR-497, NMP22, BTA, Fibrin/FDP etc. These biomarkers are often used for screening, detection, diagnosis, prognosis, prediction and monitoring of cancer development. Phosphatidylserine (PS) is an essential component in all human cells which is present on the inner leaflet of the cell membrane. The oxidative stress causes exposure of PS on the surface of the vascular endothelium in the cancer cells (lung, breast, pancreatic, bladder, skin, brain metastasis, rectal adenocarcinoma etc...
September 1, 2017: Seminars in Cancer Biology
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