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https://www.readbyqxmd.com/read/29793100/the-still-uncertain-identity-of-the-channel-forming-unit-s-of-the-mitochondrial-permeability-transition-pore
#1
REVIEW
Christopher P Baines, Manuel Gutiérrez-Aguilar
Mitochondria from different organisms can undergo a sudden process of inner membrane unselective leakiness to molecules known as the mitochondrial permeability transition (MPT). This process has been studied for nearly four decades and several proteins have been claimed to constitute, or at least regulate the usually inactive pore responsible for this transition. However, no protein candidate proposed as the actual pore-forming unit has passed rigorous gain- or loss-of-function genetic tests. Here we review evidence for -and against- putative channel-forming components of the MPT pore...
May 16, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29792924/creation-of-an-acellular-vaginal-matrix-for-potential-vaginal-augmentation-and-cloacal-repair
#2
K V Greco, L G Jones, I Obiri-Yeboa, T Ansari
STUDY OBJECTIVE: our aim was to use porcine vagina to create a vaginal matrix and test its cellular biocompatibility. DESIGN: vagina was harvested from pigs and de-cellularised (DC) using a combination of detergents (Triton x-100 and sodium deoxycholate) and enzymes (DNAse/RNAse). INTERVENTIONS: the presence of cellular material, collagen structural integrity and basement membrane proteins were assessed histologically. To address cytocompatibility, porcine adipose derived-mesenchymal stem cells (AD-MSC) were harvested from abdominal fat together with vaginal epithelial cells (VEC) and seeded onto the mucosal aspect of the vaginal scaffold...
May 21, 2018: Journal of Pediatric and Adolescent Gynecology
https://www.readbyqxmd.com/read/29792904/monoclonal-antibody-dl11c8-identifies-adam23-as-a-component-of-lipid-raft-microdomains
#3
Zaine L M Borgonovo, Caroline F Ribeiro, Michele D M Costa, Ingrid L M Souza, Gustavo R Rossi, Monica V Alcantara, Max Ingberman, Luciano G Braga, Adriana F Mercadante, Lia S Nakao, Silvio M Zanata
A disintegrin and metalloprotease protein 23 (ADAM23) is a transmembrane type I glycoprotein involved with the development and maintenance of the nervous system, including neurite outgrowth, neuronal adhesion and differentiation and regulation of synaptic transmission. In addition, ADAM23 seems to participate in immune response and tumor establishment through interaction with different members of integrin receptors. Here, we describe a novel monoclonal antibody (DL11C8) that specifically recognizes the cysteine-rich domain of both pre-protein (100kDa) and mature (70 kDa) forms of ADAM23 from different species, including human, rodents and avian orthologs...
May 21, 2018: Neuroscience
https://www.readbyqxmd.com/read/29792810/optogenetic-inhibition-of-g%C3%AE-q-protein-signaling-reduces-calcium-oscillation-stochasticity
#4
Pimkhuan Hannanta-Anan, Brian Y Chow
As fast terminators of G-protein coupled receptor (GPCR) signaling, regulators of G-protein signaling (RGS) serve critical roles in fine-tuning second messenger levels and, consequently, cellular responses to external stimuli. Here, we report the creation of an optogenetic RGS2 (opto-RGS2) that suppresses agonist-evoked calcium oscillations by the inactivation of Gαq protein. In this system, cryptochrome-mediated hetero-dimerization of the catalytic RGS2-box with its N-terminal amphipathic helix reconstitutes a functional membrane-localized complex that can dynamically suppress store-operated release of calcium...
May 24, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29792687/co-mobility-of-gabarap-and-phosphatidylinositol-4-kinase-2a-on-cytoplasmic-vesicles
#5
Yan Chen, Hui-Qiao Sun, John P Eichorst, Joseph P Albanesi, Helen Yin, Joachim D Mueller
We previously reported that recruitment of the Type IIA phosphatidylinositol 4-kinase (PI4K2A) to autophagosomes by GABARAP, a member of the Atg8 family of autophagy-related proteins, is important for autophagosome-lysosome fusion. Because both PI4K2A and GABARAP have also been implicated in the intracellular trafficking of plasma membrane receptors in the secretory/endocytic pathway, we characterized their interaction in cells under non-autophagic conditions. Fluorescence fluctuation spectroscopy measurements revealed that GABARAP exists predominantly as a cytosolic monomer in live cells, but is recruited to small cytoplasmic vesicles upon overexpression of PI4K2A...
May 24, 2018: Biochemistry
https://www.readbyqxmd.com/read/29792401/synthetic-single-domain-antibodies-for-the-conformational-trapping-of-membrane-proteins
#6
Iwan Zimmermann, Pascal Egloff, Cedric Aj Hutter, Fabian M Arnold, Peter Stohler, Nicolas Bocquet, Melanie N Hug, Sylwia Huber, Martin Siegrist, Lisa Hetemann, Jennifer Gera, Samira Gmür, Peter Spies, Daniel Gygax, Eric R Geertsma, Roger Jp Dawson, Markus A Seeger
Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies. To target the limited hydrophilic surfaces of membrane proteins, we designed three sybody libraries that exhibit different shapes and moderate hydrophobicity of the randomized surface...
May 24, 2018: ELife
https://www.readbyqxmd.com/read/29792376/somatic-ace-regulates-self-renewal-of-mouse-spermatogonial-stem-cells-via-the-mapk-signaling-pathway
#7
Tingting Gao, Xin Zhao, Chenchen Liu, Binbin Shao, Xi Zhang, Kai Li, Jinyang Cai, Su Wang, Xiaoyan Huang
Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs...
May 24, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29792307/putative-vaccine-candidates-and-drug-targets-identified-by-reverse-vaccinology-and-subtractive-genomics-approaches-to-control-haemophilus-ducreyi-the-causative-agent-of-chancroid
#8
Alissa de Sarom, Arun Kumar Jaiswal, Sandeep Tiwari, Letícia de Castro Oliveira, Debmalya Barh, Vasco Azevedo, Carlo Jose Oliveira, Siomar de Castro Soares
Chancroid is a sexually transmitted infection (STI) caused by the Gram-negative bacterium Haemophilus ducreyi The control of chancroid is difficult and the only current available treatment is antibiotic therapy; however, antibiotic resistance has been reported in endemic areas. Owing to recent outbreaks of STIs worldwide, it is important to keep searching for new treatment strategies and preventive measures. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine and drug targets against 28 strains of H...
May 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29792170/liddle-s-like-syndrome-associated-with-nephrotic-syndrome-secondary-to-membranous-nephropathy-the-first-case-report
#9
Eriko Yamaguchi, Kazuhiro Yoshikawa, Izaya Nakaya, Karen Kato, Yoshikazu Miyasato, Terumasa Nakagawa, Yutaka Kakizoe, Masashi Mukoyama, Jun Soma
BACKGROUND: Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel (ENaC) β or γ subunits. Patients with this syndrome present with early onset of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronism, and a potassium-sparing diuretics (triamterene or amiloride) can drastically improves the disease condition. Although elderly patients having these characteristics were considered to have Liddle's syndrome or Liddle's-like syndrome, no previous report has indicated that Liddle's-like syndrome could be caused by nephrotic syndrome of primary glomerular disease, which is characterized by urinary excretion of > 3 g of protein/day plus edema and hypoalbuminemia, or has explained how the activity function of ENaC could be affected in the setting of high proteinuria...
May 23, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29792169/use-of-synthetic-adrenocorticotropic-hormone-in-patients-with-iga-nephropathy
#10
Bhanu Prasad, Shelley Giebel, Michelle C E McCarron, Nelson Leung
BACKGROUND: Synthetic adrenocorticotropic hormone (ACTH) has been demonstrated to be effective in patients with membranous nephropathy, minimal change disease and some histological subtypes of focal segmental glomerulosclerosis. Its clinical impact in patients with IgA nephropathy is currently unclear. CASE PRESENTATION: In this report, we describe the clinical use of ACTH in patients with IgA nephropathy. Three female patients (24-44 years) with overt proteinuria received intramuscular (IM) ACTH for varying time periods (8-14 months)...
May 23, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29792024/metabotropic-glutamate-receptors-in-alcohol-use-disorder-physiology-plasticity-and-promising-pharmacotherapies
#11
Max E Joffe, Samuel W Centanni, Anel A Jaramillo, Danny G Winder, P Jeffrey Conn
Developing efficacious treatments for alcohol use disorder (AUD) has proven difficult. The insidious nature of the disease necessitates a deep understanding of its underlying biology as well as innovative approaches to ameliorate ethanol-related pathophysiology. Excessive ethanol-seeking and relapse are generated by long-term changes to membrane properties, synaptic physiology, and plasticity throughout the limbic system and associated brain structures. Each of these factors can be modulated by metabotropic glutamate (mGlu) receptors, a diverse set of G protein-coupled receptors highly expressed throughout the central nervous system...
May 23, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29791976/a-cipk-protein-kinase-targets-sucrose-transporter-mdsut2-2-at-ser-254-for-phosphorylation-to-enhance-salt-tolerance
#12
Qi-Jun Ma, Mei-Hong Sun, Hui Kang, Jing Lu, Chun-Xiang You, Yu-Jin Hao
Soil salinity is one of the major abiotic stressors that negatively affect crop growth and yield. Salt stress can regulate antioxidants and the accumulation of osmoprotectants. In the study, a sucrose transporter MdSUT2.2 was identified in apple. Overexpression of MdSUT2.2 gene increased salt tolerance in the transgenic apple, compared with the WT control 'Gala'. In addition, it was found that protein MdSUT2.2 was phosphorylated at Ser254 site in response to salt. A DUAL membrane yeast hybridization system through an apple cDNA library demonstrated that a protein kinase MdCIPK13 interacted with MdSUT2...
May 23, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29791842/plant-endocytosis-requires-the-er-membrane-anchored-proteins-vap27-1-and-vap27-3
#13
Giovanni Stefano, Luciana Renna, Clarissa Wormsbaecher, Jessie Gamble, Krzysztof Zienkiewicz, Federica Brandizzi
Through yet-undefined mechanisms, the plant endoplasmic reticulum (ER) has a critical role in endocytosis. The plant ER establishes a close association with endosomes and contacts the plasma membrane (PM) at ER-PM contact sites (EPCSs) demarcated by the ER membrane-associated VAMP-associated-proteins (VAP). Here, we investigated two plant VAPs, VAP27-1 and VAP27-3, and found an interaction with clathrin and a requirement for the homeostasis of clathrin dynamics at endocytic membranes and endocytosis. We also demonstrated direct interaction of VAP27-proteins with phosphatidylinositol-phosphate lipids (PIPs) that populate endocytic membranes...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791777/counting-on-death-quantitative-aspects-of-bcl-2-family-regulation
#14
REVIEW
Annika Hantusch, Markus Rehm, Thomas Brunner
The Bcl-2 protein family members critically regulate mitochondrial outer membrane permeabilization (MOMP), a point-of-no-return in the intrinsic and extrinsic apoptosis pathways. The common view on qualitative interaction and activation patterns of the three subclasses, the BH3-only proteins, prosurvivals and effectors, is static and currently being revolutionized by an emerging understanding of the complex dynamic equilibria that govern cellular fate. Recent experimental evidence on protein associations with the mitochondrial outer membrane, retrotranslocation to the cytosol and differential binding affinities in aqueous and membranous environments instigate the development of a revised model of Bcl-2 family interplay...
May 23, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29791141/fluorogenic-probing-of-membrane-protein-trafficking
#15
Chenge Li, Aurélien Mourton, Marie-Aude Plamont, Vanessa Rodrigues, Isabelle Aujard, Michel Volovitch, Thomas Le Saux, Franck Perez, Sophie Vriz, Ludovic Jullien, Alain Joliot, Arnaud Gautier
Methods to differentially label cell-surface and intracellular membrane proteins are indispensable for understanding their function and the regulation of their trafficking. We present an efficient strategy for the rapid and selective fluorescent labeling of membrane proteins based on the chemical-genetic fluorescent marker FAST (fluorescence-activating and absorption-shifting tag). Cell-surface FAST-tagged proteins could be selectively and rapidly labeled using fluorogenic membrane-impermeant 4-hydroxybenzylidene rhodanine (HBR) analogs...
May 23, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29791140/correlative-stimulated-emission-depletion-and-scanning-ion-conductance-microscopy
#16
Philipp Hagemann, Astrid Gesper, Patrick Happel
Correlation microscopy combining fluorescence and scanning probe or electron microscopy is limited to fixed samples due to the sample preparation and non-physiological imaging conditions required by most probe or electron microscopy techniques. Among the few scanning probe techniques that allow imaging of living cells under physiological conditions, Scanning Ion Conductance Microscopy (SICM) has been shown to be the technique which minimizes the impact on the investigated sample. However, combinations of SICM and fluorescence microscopy suffered from the mismatch in resolution due to the limited resolution of conventional light microscopy...
May 23, 2018: ACS Nano
https://www.readbyqxmd.com/read/29790985/the-way-is-the-goal-how-seca-transports-proteins-across-the-cytoplasmic-membrane-in-bacteria
#17
Tamar Cranford-Smith, Damon Huber
In bacteria, translocation of most soluble secreted proteins (and outer membrane proteins in Gram-negative bacteria) across the cytoplasmic membrane by the Sec machinery is mediated by the essential ATPase SecA. At its core, this machinery consists of SecA and the integral membrane proteins SecYEG, which form a protein conducting channel in the membrane. Proteins are recognised by the Sec machinery by virtue of an internally encoded targeting signal, which usually takes the form of an N-terminal signal sequence...
June 1, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29790984/co-translational-protein-targeting-in-bacteria
#18
Ruth Steinberg, Lara Knüpffer, Andrea Origi, Rossella Asti, Hans-Georg Koch
About 30% of all bacterial proteins execute their function outside of the cytosol and have to be transported into or across the cytoplasmic membrane. Bacteria use multiple protein transport systems in parallel, but the majority of proteins engage two distinct targeting systems. One is the co-translational targeting by two universally conserved GTPases, the signal recognition particle (SRP) and its receptor FtsY, which deliver inner membrane proteins to either the SecYEG translocon or the YidC insertase for membrane insertion...
June 1, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29790963/the-presenilin-loop-region-is-essential-for-glycogen-synthase-kinase-3-beta-mediated-functions-on-motor-proteins-during-axonal-transport
#19
Rupkatha Banerjee, Zoe Rudloff, Crystal Naylor, Michael Yu, Shermali Gunawardena
Neurons require intracellular transport of essential components for function and viability, and defects in transport has been implicated in many neurodegenerative diseases including Alzheimer's disease (AD). One possible mechanism by which transport defects could occur is by improper regulation of molecular motors. Previous work showed that reduction of Presenilin (PS) or Glycogen synthase kinase 3 beta (GSK3β) stimulated APP vesicle motility. Excess GSK3β caused transport defects and increased motor binding to membranes, while reduction of PS decreased active GSK3β and motor binding to membranes...
May 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29790818/endosomal-and-phagosomal-snares
#20
Ilse Dingjan, Peter T A Linders, Danielle R J Verboogen, Natalia H Revelo, Martin Ter Beest, Geert van den Bogaart
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes with other endosomes, lysosomes, the Golgi apparatus, the plasma membrane, and the endoplasmic reticulum. The goal of this review is to provide an overview of the SNAREs involved in endosomal and phagosomal trafficking...
July 1, 2018: Physiological Reviews
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