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Endocytosis, signal transduction

Yunhao Tan, Jonathan C Kagan
The receptors of the mammalian innate immune system are designed for rapid microbial detection, and are located in organelles that are conducive to serve these needs. However, emerging evidence indicates that the sites of microbial detection are not the sites of innate immune signal transduction. Rather, microbial detection triggers the movement of receptors to regions of the cell where factors called sorting adaptors detect active receptors and promote downstream inflammatory responses. These findings highlight the critical role that membrane trafficking pathways play in the initiation of innate immunity to infection...
October 12, 2016: Traffic
Stefanie Dinner, Julian Kaltschmidt, Carolin Stump-Guthier, Svetlana Hetjens, Hiroshi Ishikawa, Tobias Tenenbaum, Horst Schroten, Christian Schwerk
Listeria monocytogenes, a Gram-positive bacterium, can cause meningitis after invading the human central nervous system. The blood-cerebrospinal fluid barrier (BCSFB), located at the epithelium of the choroid plexus, is a possible entry site for L. monocytogenes into the brain, and in vitro L. monocytogenes invades human choroid plexus epithelial papilloma (HIBCPP) cells. Although host cell signal transduction subsequent to infection by L. monocytogenes has been investigated, the role of mitogen-activated protein kinases (MAPK) is not clarified yet...
September 23, 2016: Microbes and Infection
Toshiaki Tanaka, Kaoru Goto, Mitsuyoshi Iino
The exocyst complex is a large conserved hetero-oligomeric complex that consists of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84 subunits. It has been implicated in the targeting of vesicles for regulated exocytosis in various cell types, and is also important for targeted exocytosis of post-Golgi transport vesicles to the plasma membrane. The exocyst complex is essential for membrane growth, secretion and function during exocytosis and endocytosis. Moreover, the individual components of the complex are thought to act on specific biological processes, such as cytokinesis, ciliogenesis, apoptosis, autophagy and epithelial-mesenchymal transition (EMT)...
September 26, 2016: Journal of Cellular Physiology
Xiaowu Gu, Alaina M Reagan, Mark E McClellan, Michael H Elliott
Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis...
September 21, 2016: Progress in Retinal and Eye Research
Fadil M Hannan, Valerie N Babinsky, Rajesh V Thakker
The extracellular calcium (Ca(2+) o)-sensing receptor (CaSR) is a family C G protein-coupled receptor, which detects alterations in Ca(2+) o concentrations and modulates parathyroid hormone secretion and urinary calcium excretion. The central role of the CaSR in Ca(2+) o homeostasis has been highlighted by the identification of mutations affecting the CASR gene on chromosome 3q21.1. Loss-of-function CASR mutations cause familial hypocalciuric hypercalcaemia (FHH), whereas gain-of-function mutations lead to autosomal dominant hypocalcaemia (ADH)...
October 2016: Journal of Molecular Endocrinology
Nan Li, Yong Yang, Kangmin He, Fayun Zhang, Libo Zhao, Wei Zhou, Jinghe Yuan, Wei Liang, Xiaohong Fang
Smad3 is an intracellular protein that plays a key role in propagating transforming growth factor β (TGF-β) signals from cell membrane to nucleus. However whether the transient process of Smad3 activation occurs on cell membrane and how it is regulated remains elusive. Using advanced live-cell single-molecule fluorescence microscopy to image and track fluorescent protein-labeled Smad3, we observed and quantified, for the first time, the dynamics of individual Smad3 molecules docking to and activation on the cell membrane...
2016: Scientific Reports
Yanling Yan, Anna P Shapiro, Brahma R Mopidevi, Muhammad A Chaudhry, Kyle Maxwell, Steven T Haller, Christopher A Drummond, David J Kennedy, Jiang Tian, Deepak Malhotra, Zi-Jian Xie, Joseph I Shapiro, Jiang Liu
BACKGROUND: We have demonstrated that cardiotonic steroids, such as ouabain, signaling through the Na/K-ATPase, regulate sodium reabsorption in the renal proximal tubule. By direct carbonylation modification of the Pro222 residue in the actuator (A) domain of pig Na/K-ATPase α1 subunit, reactive oxygen species are required for ouabain-stimulated Na/K-ATPase/c-Src signaling and subsequent regulation of active transepithelial (22)Na(+) transport. In the present study we sought to determine the functional role of Pro222 carbonylation in Na/K-ATPase signaling and sodium handling...
September 2016: Journal of the American Heart Association
Chenchang Xu, Xiuping Fu, Shaoxia Zhu, Jia-Jia Liu
Retrolinkin, a neuronal membrane protein, coordinates with endophilin A1 and mediates early endocytic trafficking and signal transduction of the ligand-receptor complex formed between brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin related Kinase B (TrkB), in dendrites of CNS (CNS) neurons. Here we report that retrolinkin interacts with the CYFIP1/2 subunit of the WAVE1 complex, a member of the WASP/WAVE family of nucleation promoting factors (NPF) that binds and activates the Arp2/3 complex to promote branched actin polymerization...
September 7, 2016: Molecular Biology of the Cell
Shaobo Wang, Haibin Liu, Xiangyang Zu, Yang Liu, Liman Chen, Xueqin Zhu, Leike Zhang, Zheng Zhou, Gengfu Xiao, Wei Wang
The host-virus interaction during the cellular entry of Japanese encephalitis virus (JEV) is poorly characterized. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates diverse cellular processes, including endocytosis and signal transduction, which may be involved in the entry of virus. Here, we showed that the proteasome inhibitors, MG132 and lactacystin, impaired the productive entry of JEV by effectively interfering with viral intracellular trafficking at the stage between crossing cell membrane and the initial translation of the viral genome after uncoating...
November 2016: Virology
Flora Guerra, Cecilia Bucci
Rab7 is a small GTPase that belongs to the Rab family and controls transport to late endocytic compartments such as late endosomes and lysosomes. The mechanism of action of Rab7 in the late endocytic pathway has been extensively studied. Rab7 is fundamental for lysosomal biogenesis, positioning and functions, and for trafficking and degradation of several signaling receptors, thus also having implications on signal transduction. Several Rab7 interacting proteins have being identified leading to the discovery of a number of different important functions, beside its established role in endocytosis...
August 18, 2016: Cells
Md Aminul Islam, Christine Große-Brinkhaus, Maren Julia Pröll, Muhammad Jasim Uddin, Sharmin Aqter Rony, Dawit Tesfaye, Ernst Tholen, Michael Hölker, Karl Schellander, Christiane Neuhoff
BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important viral diseases affecting swine industry worldwide. Despite routine farm vaccination, effective control strategies for PRRS remained elusive which underscores the need for in-depth studies to gain insight into the host immune response to vaccines. The current study aimed to investigate transcriptional responses to PRRS Virus (PRRSV) vaccine in the peripheral blood mononuclear cells (PBMCs) within 3 days following vaccination in German Landrace pigs...
2016: BMC Genomics
Jing Jiang, Lihou Dong, Lei Wang, Ling Wang, Jing Zhang, Fang Chen, Xiuli Zhang, Min Huang, Shenjun Li, Weiwei Ma, Qiaoyu Xu, Changjiang Huang, Jianmin Fang, Chunhua Wang
HER2 targeted delivery of ovarian cancer therapy has been beneficial for some patients, although, its efficacy is yet to be confirmed in large populations. We generated a novel anti-HER2 humanized antibody (Hertuzumab) and conjugated it to a microtubule-disrupting drug monomethyl auristatin E conjugate (MMAE) with a lysosomal protease-cleavable valine-citrulline linker. The average drug to antibody ratio (DAR) of Hertuzumab-vc-MMAE was varied by conjugating Hertuzumab antibodies with increasing linker-drugs (LDs) from D0-D8...
October 10, 2016: European Journal of Pharmaceutical Sciences
Jaroslaw Cendrowski, Agnieszka Mamińska, Marta Miaczynska
Signaling of plasma membrane receptors can be regulated by endocytosis at different levels, including receptor internalization, endocytic sorting towards degradation or recycling, and using endosomes as mobile signaling platforms. Increasing number of reports underscore the importance of endocytic mechanisms for signaling of cytokine receptors. In this short review we present both consistent and conflicting data regarding endocytosis and its role in signaling of receptors from the tumor necrosis factor receptor superfamily (TNFRSF) and those for interleukins (ILRs) and interferons (IFNRs)...
July 16, 2016: Cytokine & Growth Factor Reviews
Mark Windheim
Interleukin-1 (IL-1) binding to its receptor triggers signaling events at the plasma membrane that are essential but not sufficient for the induction of the IL-1-dependent gene expression. In addition, the ligand-induced endocytosis of the IL-1 receptor and signaling events that are initiated after the internalization of the IL-1 receptor presumably involving signaling endosomes are critical for the IL-1-induced gene expression. In this study, we investigate the role of membrane domains, commonly denoted as lipid rafts, in the IL-1-induced signal transduction...
October 2016: Cellular Signalling
G V Sharonov, M N Balatskaya, V A Tkachuk
Glycosylphosphatidylinositol-anchored proteins (GPI-AP) are important players in reception and signal transduction, cell adhesion, guidance, formation of immune synapses, and endocytosis. At that, a particular GPI-AP can have different activities depending on a ligand. It is known that GPI-AP oligomer creates a lipid raft in its base on plasma membrane, which serves as a signaling platform for binding and activation of src-family kinases. Yet, this does not explain different activities of GPI-APs. Meanwhile, it has been shown that short-lived actomyosin complexes are bound to GPI-APs through lipid rafts...
June 2016: Biochemistry. Biokhimii︠a︡
Bingqian Guo, Brian J McMillan, Stephen C Blacklow
The Notch signaling pathway has a critical role in cell fate determination and tissue homeostasis in a variety of different lineages. In the context of normal Notch signaling, the Notch receptor of the 'signal-receiving' cell is activated in trans by a Notch ligand from a neighboring 'signal-sending' cell. Genetic studies in several model organisms have established that ubiquitination of the Notch ligand, and its regulated endocytosis, is essential for transmission of this activation signal. In mammals, this ubiquitination step is dependent on the protein Mind bomb 1 (Mib1), a large multi-domain RING-type E3 ligase, and its direct interaction with the intracellular tails of Notch ligand molecules...
June 7, 2016: Current Opinion in Structural Biology
Luciane Martins, Adriana Franco Paes Leme, Kamila Rosamilia Kantovitz, Enilson Antonio Sallum, Márcio Zaffalon Casati, Francisco Humberto Nociti Junior
Basic, pre-clinical and clinical studies have documented the potential of amelogenin, and its variants, to affect cell response and tissue regeneration. However, the mechanisms are unclear. Thus, the aim of the present study was to identify, in cementoblasts, novel binding partners for an alternatively spliced amelogenin form (Leucine-Rich Amelogenin Peptide - LRAP), which is supposed to act as a signaling molecule in epithelial-mesenchymal interactions. LRAP-binding protein complexes from immortalized murine cementoblasts (OCCM-30) were achieved by capture affinity assay (GST pull down) and proteins present in these complexes were identified by mass spectrometry and immunoblotting...
June 9, 2016: Journal of Cellular Physiology
Yao-Wen Jiang, Hao-Yue Guo, Zhan Chen, Zhi-Wu Yu, Zhifei Wang, Fu-Gen Wu
Lipid rafts are highly ordered small microdomains mainly composed of glycosphingolipids, cholesterol, and protein receptors. Optically distinguishing lipid raft domains in cell membranes would greatly facilitate the investigations on the structure and dynamics of raft-related cellular behaviors, such as signal transduction, membrane transport (endocytosis), adhesion, and motility. However, current strategies about the visualization of lipid raft domains usually suffer from the low biocompatibility of the probes, invasive detection, or ex situ observation...
July 5, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Vicent Llopis-Torregrosa, Alba Ferri-Blázquez, Anna Adam-Artigues, Emilie Deffontaines, G Paul H van Heusden, Lynne Yenush
Cell viability requires adaptation to changing environmental conditions. Ubiquitin-mediated endocytosis plays a crucial role in this process, because it provides a mechanism to remove transport proteins from the membrane. Arrestin-related trafficking proteins are important regulators of the endocytic pathway in yeast, facilitating selective ubiquitylation of target proteins by the E3 ubiquitin ligase, Rsp5. Specifically, Rod1 (Art4) has been reported to regulate the endocytosis of both the Hxt1, Hxt3, and Hxt6 glucose transporters and the Jen1 lactate transporter...
July 15, 2016: Journal of Biological Chemistry
Ana Carolina Ferreira Cardoso, Luciana Nogueira de Sousa Andrade, Silvina Odete Bustos, Roger Chammas
Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival...
2016: Frontiers in Oncology
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