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Small membrane protein regulator

Qingfen Yu, Sameh Othman, Sabyasachi Dasgupta, Thorsten Auth, Gerhard Gompper
Nanoparticles in biological systems encounter lipid-bilayer membranes as barriers. They interact with plasma membranes, membranous organelles, such as the endoplasmic reticulum and the Golgi apparatus, the nucleus, and intracellular and extracellular vesicles, such as autophagosomes, lysosomes, and exosomes. Extracellular vesicles have recently attracted particular attention, as they are involved in the transmission of biological signals and as regulators for biological processes. For example, exosomes, small vesicles containing proteins, mRNA, and miRNA, that are released by cells into the extracellular environment, have been suggested to participate in tumor metastasis...
March 22, 2018: Nanoscale
Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Marija Adzic, Nadezda Nedeljkovic
CD73 is a bifunctional glycosylphosphatidylinositol (GPI)-anchored membrane protein which functions as ecto-5'-nucleotidase and a membrane receptor for extracellular matrix protein (ECM). A large body of evidence demonstrates a critical involvement of altered purine metabolism and particularly, increased expression of CD73 in a number of human disorders, including cancer and immunodeficiency. Massive up-regulation of CD73 was also found in reactive astrocytes in several experimental models of human neuropathologies...
2018: Frontiers in Pharmacology
Sol Sotillos, Mario Aguilar-Aragon, James Castelli-Gair Hombría
RhoGAP proteins control the precise regulation of the ubiquitous small RhoGTPases. The Drosophila Crossveinless-c (Cv-c) RhoGAP is homologous to the human tumour suppressor proteins Deleted in Liver Cancer 1-3 (DLC1-3) sharing an identical arrangement of SAM, GAP and START protein domains. Here we analyse in Drosophila the requirement of each Cv-c domain to its function and cellular localization. We show that the basolateral membrane association of Cv-c is key for its epithelial function and find that the GAP domain targeted to the membrane can perform its RhoGAP activity independently of the rest of the protein, implying the SAM and START domains perform regulatory roles...
March 15, 2018: Scientific Reports
Shyam Nyati, Nauman Chaudhry, Areeb Chatur, Brandon S Gregg, Lauren Kimmel, Dheeraj Khare, Venkatesha Basrur, Dipankar Ray, Alnawaz Rehemtulla
Post-translational K63-linked poly-ubiquitination of AKT is required for its membrane recruitment and phosphorylation dependent activation in response to growth-factor stimulation. Current assays for target specific poly-ubiquitination involve cumbersome enzymatic preparations and semi-quantitative readouts. We have engineered a reporter that can quantitatively and in a target specific manner report on AKT-directed K63-polyubiquitination (K63UbR) in live cells. The reporter constitutes the AKT-derived poly-ubiquitination substrate peptide, a K63 poly-ubiquitin binding domain (UBD) as well as the split luciferase protein complementation domains...
February 16, 2018: Oncotarget
Xiaoxing Kou, Xingtian Xu, Chider Chen, Maria Laura Sanmillan, Tao Cai, Yanheng Zhou, Claudio Giraudo, Anh Le, Songtao Shi
Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs...
March 14, 2018: Science Translational Medicine
Jerry C Madukwe, Elisabeth E Garland-Kuntz, Angeline M Lyon, Alan V Smrcka
Phospholipase C (PLC) enzymes hydrolyze membrane phosphatidylinositol 4,5 bisphosphate (PIP2) and regulate Ca2+ and protein kinase signaling in virtually all mammalian cell types. Chronic activation of the PLCɛ isoform downstream of G protein-coupled receptors (GPCRs) contributes to the development of cardiac hypertrophy. We have previously shown that PLCε-catalyzed hydrolysis of Golgi-associated phosphatidylinositol 4-phosphate (PI4P) in cardiac myocytes depends on G protein βγ subunits released upon stimulation with endothelin-1...
March 13, 2018: Journal of Biological Chemistry
Ulrich Hohmann, Julia Santiago, Joël Nicolet, Vilde Olsson, Fabio M Spiga, Ludwig A Hothorn, Melinka A Butenko, Michael Hothorn
Plant-unique membrane receptor kinases with leucine-rich repeat ectodomains (LRR-RKs) can sense small molecule, peptide, and protein ligands. Many LRR-RKs require SERK-family coreceptor kinases for high-affinity ligand binding and receptor activation. How one coreceptor can contribute to the specific binding of distinct ligands and activation of different LRR-RKs is poorly understood. Here we quantitatively analyze the contribution of SERK3 to ligand binding and activation of the brassinosteroid receptor BRI1 and the peptide hormone receptor HAESA...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Anna Maikova, Johann Peltier, Pierre Boudry, Eliane Hajnsdorf, Nicolas Kint, Marc Monot, Isabelle Poquet, Isabelle Martin-Verstraete, Bruno Dupuy, Olga Soutourina
Clostridium difficile, a major human enteropathogen, must cope with foreign DNA invaders and multiple stress factors inside the host. We have recently provided an experimental evidence of defensive function of the C. difficile CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system important for its survival within phage-rich gut communities. Here, we describe the identification of type I toxin-antitoxin (TA) systems with the first functional antisense RNAs in this pathogen...
February 26, 2018: Nucleic Acids Research
Pi Liu, Yan Zhao, Xiaoguo Liu, Jixue Sun, Dede Xu, Yang Li, Qian Li, Lihua Wang, Sichun Yang, Chunhai Fan, Jianping Lin
Shape reconfiguration of membrane protein channels is highly regulated under physiological conditions for gated transportation. Nevertheless, mechanistic understanding of molecular channels remains challenging due to the difficulty in probing gating-associated subtle structural changes. Here we show that charge neutralization can drive shape reconfiguration of a biomimetic 6-helix bundle DNA nanotube (6HB). Specifically, 6HB adopts a compact state when being neutralized by Mg2+; and monovalent ions (Na+) switch it to the expansion state, as revealed by molecular dynamics (MD) simulation, small angle X-ray scattering (SAXS) and Förster resonance energy transfer (FRET) characterization...
March 12, 2018: Angewandte Chemie
Kohei Omachi, Misato Kamura, Keisuke Teramoto, Haruka Kojima, Tsubasa Yokota, Shota Kaseda, Jun Kuwazuru, Ryosuke Fukuda, Kosuke Koyama, Shingo Matsuyama, Keishi Motomura, Tsuyoshi Shuto, Mary Ann Suico, Hirofumi Kai
Alport syndrome is a hereditary glomerular disease caused by mutation in type IV collagen α3-α5 chains (α3-α5(IV)), which disrupts trimerization, leading to glomerular basement membrane degeneration. Correcting the trimerization of α3/α4/α5 chain is a feasible therapeutic approach, but is hindered by lack of information on the regulation of intracellular α(IV) chain and the absence of high-throughput screening (HTS) platforms to assess α345(IV) trimer formation. Here, we developed sets of split NanoLuc-fusion α345(IV) proteins to monitor α345(IV) trimerization of wild-type and clinically associated mutant α5(IV)...
February 21, 2018: Cell Chemical Biology
Alanna Sedgwick, M Olivia Balmert, Crislyn D'Souza-Schorey
Aberrant cellular cholesterol accumulation contributes to the pathophysiology of many diseases including neurodegenerative disorders such as Niemann-Pick Type C (NPC) and Alzheimer's Disease1-4 . Many aspects of cholesterol efflux from cells remain elusive. Here we describe the utility of cholesterol-rich giant plasma membrane vesicles (GPMVs) as a means to monitor cholesterol that is translocated to the plasma membrane for secretion. We demonstrate that small molecules known to enhance lipid efflux, including those in clinical trials for lipid storage disorders, enhance this GPMV formation...
March 6, 2018: Experimental Cell Research
Jianxin Wei, Su Dong, Kangning Yao, Maria Francesca Ysabelle M Martinez, Paine R Fleisher, Yutong Zhao, Haichun Ma, Jing Zhao
Ubiquitin E3 ligases mediate ubiquitination and degradation of intracellular proteins. We have shown that a relatively new Skp, Cullin, F-box (SCF) protein E3 ligase, SCF FBXL19, has an anti-inflammatory effect and controls actin cytoskeleton dynamics via targeting cell membrane receptor and small GTPases for their ubiquitination and degradation, but the molecular regulation of its subunit FBXL19 stability remains unclear. Here we show that FBXL19 degradation is controlled by the balance between its ubiquitination and acetylation...
March 9, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
N-N Song, H-L Lu, C Lu, L Tong, S-Q Huang, X Huang, J Chen, Y-C Kim, W-X Xu
BACKGROUND: A major complication related to gastrointestinal (GI) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility...
March 9, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Edmond Y Huang, Milton To, Erica Tran, Lorraine T Ador Dionisio, Hyejin J Cho, Katherine L M Baney, Camille I Pataki, James A Olzmann
Endoplasmic reticulum (ER)-associated degradation (ERAD) mediates the proteasomal clearance of proteins from the early secretory pathway. In this process, ubiquitinated substrates are extracted from membrane-embedded dislocation complexes by the AAA ATPase VCP and targeted to the cytosolic 26S proteasome. In addition to its well-established role in the degradation of misfolded proteins, ERAD also regulates the abundance of key proteins such as enzymes involved in cholesterol synthesis. However, due to the lack of generalizable methods, our understanding of the scope of proteins targeted by ERAD remains limited...
March 7, 2018: Molecular Biology of the Cell
Balaje Vijayaraghavan, Ricardo A Figueroa, Cecilia Bergqvist, Amit J Gupta, Paulo Sousa, Einar Hallberg
Samp1, spindle associated membrane protein 1, is a type II integral membrane protein localized in the inner nuclear membrane. Recent studies have shown that the inner nuclear membrane protein, Emerin and the small monomeric GTPase, Ran are direct binding partners of Samp1. Here we addressed the question whether Ran could regulate the interaction between Samp1 and Emerin in the inner nuclear membrane. To investigate the interaction between Samp1 and Emerin in live cells, we performed FRAP experiments in cells overexpressing YFP-Emerin...
March 3, 2018: Biochimica et Biophysica Acta
Rhian F Walther, Mubarik Burki, Noelia Pinal, Clare Rogerson, Franck Pichaud
In Drosophila epithelial cells, apical exclusion of Bazooka/Par3 defines the position of the Zonula Adherens (ZA), which demarcates the apical and lateral membrane and allows cells to assemble into sheets. Here, we show that the small GTPase Rap1, its effector AF6/Canoe (Cno) and the Cdc42-effector Pak4/Mushroom bodies tiny (Mbt), converge in regulating epithelial morphogenesis by coupling stabilization of the Adherens Junction (AJ) protein E-Cadherin, and Bazooka retention at the ZA Furthermore, our results show that the localization of Rap1, Cno and Mbt at the ZA is interdependent, indicating their functions during ZA morphogenesis are interlinked...
March 5, 2018: Journal of Cell Science
Duarte Mateus, Elettra Sara Marini, Cinzia Progida, Oddmund Bakke
The Endoplasmic Reticulum (ER) is a membranous organelle with diverse structural and functional domains. Peripheral ER includes interconnected tubules, and dense tubular arrays called "ER matrices" together with bona fide flat cisternae. Transitions between these states are regulated by membrane-associated proteins and cytosolic factors. Recently, the small GTPases Rab10 and Rab18 were reported to control ER shape by regulating ER dynamics and fusion. Here, we present evidence that another Rab protein, Rab7a, modulates the ER morphology by controlling the ER homeostasis and ER stress...
March 2, 2018: Biochimica et Biophysica Acta
Dacheng Liang
The reactive oxygen species, generally labeled toxic due to high reactivity without target specificity, are gradually uncovered as signaling molecules involved in a myriad of biological processes. But one important feature of ROS roles in macromolecule movement has not caught attention until recent studies with technique advance and design elegance have shed lights on ROS signaling for intercellular and interorganelle communication. This review begins with the discussions of genetic and chemical studies on the regulation of symplastic dye movement through intercellular tunnels in plants (plasmodesmata), and focuses on the ROS regulatory mechanisms concerning macromolecule movement including small RNA-mediated gene silencing movement and protein shuttling between cells...
2018: Frontiers in Cell and Developmental Biology
Rosaria Meli, Claudio Pirozzi, Alessandra Pelagalli
Aquaporins (AQPs) are emerging, in the last few decades, as critical proteins regulating water fluid homeostasis in cells involved in inflammation. AQPs represent a family of ubiquitous membrane channels that regulate osmotically water flux in various tissues and sometimes the transport of small solutes, including glycerol. Extensive data indicate that AQPs, working as water channel proteins, regulate not only cell migration, but also common events essential for inflammatory response. The involvement of AQPs in several inflammatory processes, as demonstrated by their dysregulation both in human and animal diseases, identifies their new role in protection and response to different noxious stimuli, including bacterial infection...
2018: Frontiers in Physiology
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