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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/29458174/networks-that-link-cytoskeletal-regulators-and-diaphragm-proteins-underpin-filtration-function-in-drosophila-nephrocytes
#2
Simi Muraleedharan, Aksah Sam, Helen Skaer, Maneesha S Inamdar
Insect nephrocytes provide a valuable model for kidney disease, as they are structurally and functionally homologous to mammalian kidney podocytes. They possess an exceptional macromolecular assembly, the nephrocyte diaphragm (ND), which serves as a filtration barrier and helps maintain tissue homeostasis by filtering out wastes and toxic products. However, the elements that maintain nephrocyte architecture and the ND are not understood. We show that Drosophila nephrocytes have a unique cytoplasmic cluster of F-actin, which is maintained by the microtubule cytoskeleton and Rho-GTPases...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458167/autosomal-dominant-deficiency-of-the-interleukin-17f-in-recurrent-aphthous-stomatitis-possible-novel-mutation-in-a-new-entity
#3
Alireza Zare Bidoki, Ahmad Massoud, Shamsolmoulouk Najafi, Mahsa Mohammadzadeh, Nima Rezaei
Recurrent Aphthous Stomatitis (RAS) is a common oral inflammatory disease with unknown pathogenesis. Although the immune system alterations could be involved in predisposition of individuals to oral candidiasis, precise etiologies of RAS have not been understood yet. A recent study showed that autosomal dominant IL17F deficiency could cause chronic mucocutaneous candidiasis. Considering the inflammatory nature of interleukin (IL)-17F and RAS, this study was performed to check any disease-associated mutation in a number of patients with RAS...
February 16, 2018: Gene
https://www.readbyqxmd.com/read/29458124/tryptophan-mediated-dimerization-of-the-tssl-transmembrane-anchor-is-required-for-type-vi-secretion-system-activity
#4
Abdelrahim Zoued, Jean-Pierre Duneau, Eric Durand, Alexandre P España, Laure Journet, Françoise Guerlesquin, Eric Cascales
The Type VI secretion system (T6SS) is a multiprotein complex used by bacteria to deliver effectors into target cells. The T6SS comprises a bacteriophage-like contractile tail structure anchored to the cell envelope by a membrane complex constituted of the TssJ outer membrane lipoprotein and the TssL and TssM inner membrane proteins. TssJ establishes contact with the periplasmic domain of TssM whereas the transmembrane segments of TssM and its cytoplasmic domain interact with TssL. TssL protrudes in the cytoplasm but is anchored by a C-terminal transmembrane helix (TMH)...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458123/osteocyte-regulation-of-bone-and-blood
#5
REVIEW
Paola Divieti Pajevic, Daniela S Krause
This past decade has witnessed a renewed interest in the function and biology of matrix-embedded osteocytes and these cells have emerged as master regulators of bone homeostasis. They secrete two very powerful proteins, sclerostin, a Wnt-inhibitor, that suppresses bone formation, and receptor-activator of NF-kB ligand (RANKL), a cytokine required for osteoclastogenesis. Neutralizing antibodies against these proteins are currently used for the treatment of osteoporosis. Recent studies however, ascribed yet another function to osteocytes: the control of hematopoiesis and the HSPC niche, directly and through secreted factors...
February 16, 2018: Bone
https://www.readbyqxmd.com/read/29458077/reciprocal-regulation-of-the-cadherin-11-stat3-axis-by-caveolin-1-in-mouse-fibroblasts-and-lung-carcinoma-cells
#6
M Geletu, R Mohan, R Arulanandam, A Berger-Becvar, I R Nabi, P T Gunning, L Raptis
Caveolin-1 (Cav1) is an integral plasma membrane protein and a complex regulator of signal transduction. The Signal Transducer and Activator of Transcription-3 (Stat3) is activated by a number of receptor and non-receptor tyrosine kinases and is positively implicated in cancer. Despite extensive efforts, the relationship between Cav1 and Stat3 has been a matter of controversy. We previously demonstrated that engagement of E- or N-cadherin or cadherin-11 cell to cell adhesion molecules, as occurs with confluence of cultured cells, triggers a dramatic increase in the levels of tyr705 phosphorylated ie activated Stat3, by a mechanism requiring the cRac1 small GTPase...
February 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29458065/nosocomial-ventriculitis-caused-by-a-meticillin-and-linezolid-resistant-clone-of-staphylococcus-epidermidis-in-neurosurgical-patients
#7
Carlos Rodríguez-Lucas, Javier Fernández, José Antonio Boga, Lucia López-Amor, Lorena Forcelledo, Eva Lázaro-López, M Rosario Rodicio
BACKGROUND: Post-neurosurgical ventriculitis is mainly caused by coagulase-negative staphylococci. The rate of linezolid resistant S. epidermidis (LRSE) is increasing worldwide. AIMS: To report clinical and microbiological data from a series of ventriculitis cases caused by LRSE in a Spanish hospital between 2013 and 2016. METHODS: LRSE ventriculitis cases were retrospectively reviewed in a Spanish hospital during a four-year period. Clinical/epidemiological data of the infected patients were reviewed, the isolates involved were typed by PFGE and MLST, and the molecular basis of linezolid resistance was determined...
February 16, 2018: Journal of Hospital Infection
https://www.readbyqxmd.com/read/29458060/crim1-is-required-for-maintenance-of-the-ocular-lens-epithelium
#8
Oliver H Tam, David Pennisi, Lorine Wilkinson, Melissa H Little, Fatima Wazin, Victor L Wan, Frank J Lovicu
The development and growth of the vertebrate ocular lens is dependent on the regulated proliferation of an anterior monolayer of epithelial cells, and their subsequent differentiation into elongate fiber cells. The growth factor rich ocular media that bathes the lens mediates these cellular processes, and their respective intracellular signaling pathways are in turn regulated to ensure that the proper lens architecture is maintained. Recent studies have proposed that Cysteine Rich Motor Neuron 1 (Crim1), a transmembrane protein involved in organogenesis of many tissues, might influence cell adhesion, polarity and proliferation in the lens by regulating integrin-signaling...
February 16, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29457987/the-rap2c-gtpase-facilitates-b-cell-receptor-induced-reorientation-of-the-microtubule-organizing-center
#9
Jia C Wang, Jeff Y-J Lee, May Dang-Lawson, Caitlin Pritchard, Michael R Gold
When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the microtubule-organizing center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood...
February 19, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457977/single-molecule-centroid-localization-algorithm-improves-the-accuracy-of-fluorescence-binding-assays
#10
Boyang Hua, Yanbo Wang, Seongjin Park, Kyu Young Han, Digvijay Singh, Jin Hyun Kim, Wei Cheng, Taekjip Ha
Here, we demonstrate that the use of single-molecule centroid localization algorithm can improve the accuracy of fluorescence binding assays. Two major artifacts in this type of assays, i.e., non-specific binding events and optically overlapping receptors, can be detected and corrected during analysis. The effectiveness of our method was confirmed by measuring two weak biomolecular interactions, the interaction between the B1 domain of streptococcal protein G (pGB1) and immunoglobulin G (IgG), and the one between double-stranded DNA (dsDNA) and the Cas9-RNA complex with limited sequence matches...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29457815/hydrogen-bonding-effect-between-active-site-and-protein-environment-on-catalysis-performance-in-h-2-producing-nife-hydrogenases
#11
Siyao Qiu, Luis Miguel Azofra, Douglas R MacFarlane, Chenghua Sun
The interaction between the active site and the surrounding protein environment plays a fundamental role in the hydrogen evolution reaction (HER) in [NiFe] hydrogenases. Our density functional theory (DFT) findings demonstrate that the reaction Gibbs free energy required for the rate determining step decreases by 7.1 kcal mol-1 when the surrounding protein environment is taken into account, which is chiefly due to free energy decreases for the two H+ /e- addition steps (the so-called Ni-SIa to I1, and Ni-C to Ni-R), being the largest thermodynamic impediments of the whole reaction...
February 19, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29457687/substrate-binding-drives-active-site-closing-of-human-blood-group-b-galactosyltransferase-as-revealed-by-hot-spot-labeling-and-nmr-experiments
#12
Thomas Peters, Sophie Weissbach, Friedemann Flügge
Crystallography has shown that human blood group A (GTA) and B (GTB) glycosyltransferases undergo transitions between "open", "semi-closed", and "closed" conformations upon substrate binding. However, the time scales of corresponding conformational reorientations are unknown. Crystal structures show that Trp and Met residues are located at "conformational hot spots" of the enzymes. Therefore, we have utilized 15N-side chain labeling of Trp residues, and 13C-methyl labeling of Met residues to study substrate induced conformational transitions of GTB...
February 19, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29457664/production-and-structural-analysis-of-membrane-anchored-proteins-in-phospholipid-nanodiscs
#13
Kolio Raltchev, Joka Pipercevic, Franz Hagn
Structural studies on membrane-anchored proteins containing a transmembrane (TM) helix has been hampered by difficulties in producing these proteins in a natively folded form. Detergents that are required to solubilize the hydrophobic TM helix usually destabilize the soluble domain. Thus, TM helices are removed for structural studies, which neglects the pivotal role of a membrane on protein function. Here, we present a versatile strategy for the production of this protein class attached to phospholipid nanodiscs...
February 19, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29457657/semaphorin4a-and-h-ferritin-utilize-tim-1-on-human-oligodendrocytes-a-novel-neuro-immune-axis
#14
Brian Chiou, Elisabeth Lucassen, Michael Sather, Asha Kallianpur, James Connor
Deficiency of trophic factors relating to the survival of oligodendrocytes, combined with direct interactions with the immune system, are favored paradigms that are increasingly implicated in demyelinating diseases of the central nervous system. We and others have previously shown that Sema4A and H-ferritin interact through the T-cell immunoglobulin and mucin domain (Tim-2) receptor in mice. H-ferritin has been identified as the iron delivery protein for oligodendrocytes, whereas Sema4A causes a direct cytotoxic effect...
February 19, 2018: Glia
https://www.readbyqxmd.com/read/29457279/lysophosphatidylserine-suppression-of-t-cell-activation-via-gpr174-requires-g%C3%AE-s-proteins
#15
Michael J Barnes, Jason G Cyster
G protein-coupled receptors regulate diverse aspects of T cell activity and effector function. Recently, we showed that GPR174 mediates the suppression of T cell proliferation in vitro induced by the polar lipid lysophosphatidylserine (LysoPS). Here, we investigated the in vivo activity of this pathway and characterized the mechanisms involved. Using in vivo models of T cell proliferation induced by sublethal irradiation or regulatory T cell depletion, we show that GPR174 expression can constrain T cell proliferation...
February 19, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29457278/zwitterionic-nanocages-overcome-the-efficacy-loss-of-biologic-drugs
#16
Bowen Li, Zhefan Yuan, Peng Zhang, Andrew Sinclair, Priyesh Jain, Kan Wu, Caroline Tsao, Jingyi Xie, Hsiang-Chieh Hung, Xiaojie Lin, Tao Bai, Shaoyi Jiang
For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself...
February 19, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29457176/effect-of-hu-protein-on-the-conformation-and-compaction-of-dna-in-a-nanochannel
#17
Durgarao Guttula, Fan Liu, Jeroen A van Kan, Véronique Arluison, Johan R C van der Maarel
The effect of the heat unstable nucleoid structuring protein HU on the conformation of single DNA molecules confined in a nanochannel was investigated with fluorescence microscopy. Pre-incubated DNA molecules contract in the longitudinal direction of the channel with increasing concentration of HU. This contraction is mainly due to HU-mediated bridging of distal DNA segments and is controlled by channel diameter as well as ionic composition and strength of the buffer. For over-threshold concentrations of HU, the DNA molecules compact into an condensed form...
February 19, 2018: Soft Matter
https://www.readbyqxmd.com/read/29457119/effects-of-glucose-insulin-infusion-during-major-oral-and-maxillofacial-surgery-on-postoperative-complications-and-outcomes
#18
Akina Tohya, Atsushi Kohjitani, Sachi Ohno, Kaoru Yamashita, Yozo Manabe, Mitsutaka Sugimura
Background: Secretion of hormones, which antagonize the action of insulin, is facilitated in response to surgery, and acute resistance to the action of insulin develops. Our aim is to elucidate the effects of intraoperative glycemic control by glucose-insulin (GI) infusion on postoperative complications and outcomes in major oral and maxillofacial surgery. Findings: Thirty patients aged ≥ 60 years undergoing a radical operation of oral malignant tumors with tissue reconstruction (≥ 8 h) were analyzed...
2018: JA Clin Rep
https://www.readbyqxmd.com/read/29456854/novel-braf-mutation-in-melanoma-a-case-report
#19
Serena Trubini, Alessandro Ubiali, Carlo Terenzio Paties, Luigi Cavanna
In melanoma, a number of specific genetic and genomic aberrations have been identified to be important in tumorigenesis. In particular, the mutant B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) gene is the target of tailored therapy with kinase inhibitor molecules. Identification of the array of mutations in patients with melanoma will be useful in determining a genetic profile of the tumor with potential implications for treatment decisions. A rare aminoacidic insertion in codon 599 of the BRAF gene (c...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29456820/immunogenicity-of-heparin-binding-hemagglutinin-expressed-by-pichia-pastoris-gs115-strain
#20
Xindong Teng, Xiaoguang Chen, Ke Zhu, Hefei Xu
Objectives: Heparin-binding hemagglutinin (HBHA), a mycobacterial cell surface protein, mediates adhesion to nonphagocytic cells and the dissemination of Mycobacterium tuberculosis ( M. tuberculosis ) from the site of primary infection. Superior expression systems are required to obtain abundant M. tuberculosis proteins for the purpose of diagnosing M. tuberculosis infection or for the immunization. Here, HBHA was expressed by Pichia pastoris ( P. pastoris ) GS115 strain , and the immunogenicity of HBHA was evaluated...
February 2018: Iranian Journal of Basic Medical Sciences
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