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Adaptor protein 2

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https://www.readbyqxmd.com/read/28533472/yersinia-pestis-yopk-inhibits-bacterial-adhesion-to-host-cells-by-binding-to-the-extracellular-matrix-adaptor-protein-matrilin-2
#1
Yafang Tan, Wanbing Liu, Qingwen Zhang, Shiyang Cao, Haihong Zhao, Tong Wang, Zhizhen Qi, Yanping Han, Yajun Song, Xiaoyi Wang, Ruifu Yang, Zongmin Du
Pathogenic yersiniae harbor a type III secretion system (T3SS) that injects Yersinia outer protein (Yop) into host cells. YopK has been shown to control Yop translocation and prevent inflammasome recognition of T3SS by the innate immune system. Here, we demonstrate that YopK inhibits bacterial adherence to host cells by binding to the extracellular matrix adaptor protein matrilin-2 (MATN2). YopK binds to MATN2 and deleting the amino acids 91--124 disrupts binding of YopK to MATN2. A yopK null mutant exhibits hyper-adhesive phenotype, which could be responsible for the established Yop hyper-translocation phenotype of yopK mutant...
May 22, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533375/keap1-modifying-small-molecule-reveals-muted-nrf2-signaling-responses-in-neural-stem-cells-from-huntington-s-disease-patients
#2
Luisa Quinti, Sharadha Dayalan Naidu, Ulrike Träger, Xiqun Chen, Kimberly Kegel-Gleason, David Llères, Colúm Connolly, Vanita Chopra, Cho Low, Sébastien Moniot, Ellen Sapp, Adelaide R Tousley, Petr Vodicka, Michael J Van Kanegan, Linda S Kaltenbach, Lisa A Crawford, Matthew Fuszard, Maureen Higgins, James R C Miller, Ruth E Farmer, Vijay Potluri, Susanta Samajdar, Lisa Meisel, Ningzhe Zhang, Andrew Snyder, Ross Stein, Steven M Hersch, Lisa M Ellerby, Eranthie Weerapana, Michael A Schwarzschild, Clemens Steegborn, Blair R Leavitt, Alexei Degterev, Sarah J Tabrizi, Donald C Lo, Marian DiFiglia, Leslie M Thompson, Albena T Dinkova-Kostova, Aleksey G Kazantsev
The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#3
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein - apoptosis associated speck-like protein containing a caspase-activation and -recruitment domain (ASC) - activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 20, 2017: International Immunology
https://www.readbyqxmd.com/read/28529112/myeloid-differentiation-factor-88-is-up-regulated-in-epileptic-brain-and-contributes-to-experimental-seizures-in-rats
#4
Na Wang, Xiong Han, Haipeng Liu, Ting Zhao, Jie Li, Yan Feng, Xiujuan Mi, Yanke Zhang, Yanan Chen, Xuefeng Wang
Accumulating evidence supports that activation of inflammatory pathways is a crucial factor contributing to the pathogenesis of seizures. In particular, the activation of interleukin-1 beta (IL-1β) system exerts proconvulsant effects in a large variety of seizure models. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein in the signaling cascade elicited by IL-1β. The present study aimed to investigate the expression pattern of MyD88 in rat models of seizures and in patients with refractory temporal lobe epilepsy (TLE), and to study the role of MyD88 in epileptic seizures...
May 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28526927/sodium-thiosulphate-attenuates-brain-inflammation-induced-by-systemic-lipopolysaccharide-administration-in-c57bl-6j-mice
#5
Gonzalo Acero, Miryam Nava Catorce, Ricardo González-Mendoza, Marco Antonio Meraz-Rodríguez, Luis Fernando Hernández-Zimbron, Roberto González-Salinas, Goar Gevorkian
It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration...
May 19, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28526415/lnk-deficiency-aggregates-palmitate-induced-preadipocyte-apoptosis
#6
Jie-Yi Du, Chen-Chen Jin, Guo-Hao Wang, Xiong-Qing Huang, Jian-Ding Cheng, Xue-Jun Wen, Xiao-Miao Zhao, Guan-Lei Wang
LNK (SH2B3) is an intracellular adaptor protein that negatively regulates cellular proliferation or self-renewal of hematopoietic stem cells and some other progenitor cells. LNK is also recognized as a key regulator of insulin resistance and inflammatory responses in several tissues and organs. It is unknown the function of LNK in adipose tissue. We previously demonstrated that type 2 diabetes mellitus (T2DM) mouse model had elevated serum free fatty acids (FFAs) levels and increased preadipocyte apoptosis in visceral fat tissue, showing the occurrence of lipotoxicity...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28508887/an-evolutionary-switch-in-nd2-enables-src-kinase-regulation-of-nmda-receptors
#7
David P Scanlon, Alaji Bah, Mickaël Krzeminski, Wenbo Zhang, Heather L Leduc-Pessah, Yi Na Dong, Julie D Forman-Kay, Michael W Salter
The non-receptor tyrosine kinase Src is a key signalling hub for upregulating the function of N-methyl D-aspartate receptors (NMDARs). Src is anchored within the NMDAR complex via NADH dehydrogenase subunit 2 (ND2), a mitochondrially encoded adaptor protein. The interacting regions between Src and ND2 have been broadly identified, but the interaction between ND2 and the NMDAR has remained elusive. Here we generate a homology model of ND2 and dock it onto the NMDAR via the transmembrane domain of GluN1. This interaction is enabled by the evolutionary loss of three helices in bilaterian ND2 proteins compared to their ancestral homologues...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28504462/endocytic-activity-of-hiv-1-vpu-phosphoserine-dependent-interactions-with-clathrin-adaptors
#8
Charlotte A Stoneham, Rajendra Singh, Xiaofei Jia, Yong Xiong, John Guatelli
HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune-evasion, triggering ubiquitin-mediated degradation of some targets but also modulating endosomal trafficking to deplete them from the plasma membrane. Interactions between Vpu and the heterotetrameric clathrin adaptors AP-1 and AP-2 have been described, yet the molecular basis and functional roles of such interactions are incompletely defined. To investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8 α-chain...
May 14, 2017: Traffic
https://www.readbyqxmd.com/read/28494724/c-type-lectin-receptor-old-friend-and-new-player
#9
Hai Hou, Yahui Guo, Qing Chang, Tianming Luo, Xin Wu, Xueqiang Zhao
During the last two decades, C-type lectin receptors (CLRs) have been demonstrated to play key roles in initiating the host immune response upon fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2, Dectin-3 and Mincle, recognize the cell wall component from the infected microorganisms by using their carbohydrate recognition domain (CRD). Upon stimulation, CLRs induce multiple signal transduction cascades through their own immune-receptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM-containing adaptor proteins such as FcRγ, which then lead to the activation of nuclear factor kappa B (NF-kB) through Syk- and CARD9-dependent pathway...
May 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28491822/comparison-of-the-expression-changes-after-botulinum-toxin-type-a-and-minocycline-administration-in-lipopolysaccharide-stimulated-rat-microglial-and-astroglial-cultures
#10
Anna Piotrowska, Katarzyna Popiolek-Barczyk, Flaminia Pavone, Joanna Mika
Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of SNARE proteins, which prevents cells from releasing neurotransmitters from vesicles, while the effects of minocycline are related to the inhibition of p38 activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their direct impact on glial cells is not fully known. Therefore, the aim of the present study was to determine the effects of those drugs on microglial and astroglial activity after lipopolysaccharide (LPS) stimulation and their potential synergistic action...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28490631/a-split-luciferase-complementation-real-time-reporting-assay-enables-monitoring-of-the-disease-associated-transmembrane-protein-trem2-in-live-cells
#11
Megan M Varnum, Kevin A Clayton, Asuka Yoshii-Kitahara, Grant Yonemoto, Lacin Koro, Seiko Ikezu, Tsuneya Ikezu
Triggering receptor expressed on myeloid cells 2 (TREM2) is a single transmembrane molecule uniquely expressed in microglia. TREM2 mutations are genetically linked to Nasu-Hakola disease and associated with multiple neurodegenerative disorders, including Alzheimer's disease (AD). TREM2 may regulate microglial inflammation and phagocytosis through coupling to the adaptor protein, TYRO protein tyrosine kinase binding protein (TYROBP). However, there is no functional system for monitoring this protein-protein interaction...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28484272/effect-of-bacillus-subtilis-on-aeromonas-hydrophila-induced-intestinal-mucosal-barrier-function-damage-and-inflammation-in-grass-carp-ctenopharyngodon-idella
#12
Weiguang Kong, Can Huang, Ying Tang, Ding Zhang, Zhixin Wu, Xiaoxuan Chen
Our study explored the effect of oral intubation of Bacillus subtilis on Aeromonas hydrophila-induced intestinal mucosal barrier function damage and inflammation in grass carp. The mid-intestine mucosal tissue was collected for ATPase activity measurement. Intestinal mucosa was also ultrastructurally examined with transmission electron microscope (TEM), and its permeability was determined using Evans blue (EB) and D-lactic acid. The mid-intestine pro-inflammation cytokine, MyD88 and tight junction (TJ) protein mRNA expression levels were measured using real-time quantitative PCR...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479297/nkx3-2-induces-oxygen-concentration-independent-and-lysosome-dependent-degradation-of-hif-1%C3%AE-to-modulate-hypoxic-responses-in-chondrocytes
#13
Suhjean Im, Dae-Won Kim
Hypoxia-inducible factor 1-alpha (HIF-1α) is a DNA-binding transcription factor regulating hypoxic responses. It plays a key role in vascularization and angiogenesis as well as various metabolic pathways. Interestingly, during early phase endochondral ossification when HIF expression in chondrocytes is evident, developing cartilage primordia remains avascular until hypertrophic calcification commences. In this work, we uncovered a novel pathway causing oxygen concentration-independent and proteasome-independent degradation of HIF-1α protein...
May 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28468944/enac-activity-is-regulated-by-calpain-2-proteolysis-of-marcks-proteins
#14
Darrice S Montgomery, Ling Yu, Zinah M Ghazi, Tiffany L Thai, Otor Al-Khalili, He-Ping Ma, Douglas C Eaton, Abdel A Alli
We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains are a family of ubiquitously expressed intracellular Ca(2+)-dependent cysteine proteases involved in signal transduction. Here we examine the role of calpain-2 in regulating MARCKS and ENaC in cultured renal epithelial cells and in the mouse kidney...
May 3, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28466190/microglia-endocytose-amyloid-%C3%AE-through-the-binding-of-transglutaminase-2-and-milk-fat-globule-egf-factor-8-protein
#15
Kenji Kawabe, Katsura Takano, Mitsuaki Moriyama, Yoichi Nakamura
Activation of glial cells has been observed in neurodegenerative diseases including Alzheimer's disease (AD). Aggregation of amyloid β (Aβ) is profusely observed as characteristic pathology in AD brain. In our previous study using microglial cell line BV-2, tissue-type transglutaminase (TG2) was found to be involved in phagocytosis (Kawabe et al., in Neuroimmunomodulation 22(4):243-249, 2015; Kawabe et al., Neurochem Res 2017). In the present study, we examined whether TG2 and milk fat globule EGF factor 8 protein (MFG-E8), an adaptor protein promotes macrophage to engulf apoptotic cells, were involved in Aβ endocytosis...
May 3, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28465426/a-novel-agonist-of-the-trif-pathway-induces-a-cellular-state-refractory-to-replication-of-zika-chikungunya-and-dengue-viruses
#16
Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R DeFilippis
The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread...
May 2, 2017: MBio
https://www.readbyqxmd.com/read/28463985/palmitic-acid-is-a-toll-like-receptor-4-ligand-that-induces-human-dendritic-cell-secretion-of-il-1%C3%AE
#17
Dequina A Nicholas, Kangling Zhang, Christopher Hung, Shane Glasgow, Aruni Wilson Aruni, Juli Unternaehrer, Kimberly J Payne, William H R Langridge, Marino De Leon
Palmitic acid (PA) and other saturated fatty acids are known to stimulate pro-inflammatory responses in human immune cells via Toll-like receptor 4 (TLR4). However, the molecular mechanism responsible for fatty acid stimulation of TLR4 remains unknown. Here, we demonstrate that PA functions as a ligand for TLR4 on human monocyte derived dendritic cells (MoDCs). Hydrophobicity protein modeling indicated PA can associate with the hydrophobic binding pocket of TLR4 adaptor protein MD-2. Isothermal titration calorimetry quantified heat absorption that occurred during PA titration into TLR4/MD2, indicating that PA binds to TLR4/MD2...
2017: PloS One
https://www.readbyqxmd.com/read/28462384/trif-differentially-regulates-hepatic-steatosis-and-inflammation-fibrosis-in-mice
#18
Ling Yang, Kouichi Miura, Bi Zhang, Hiroshi Matsushita, Yoon Mee Yang, Shuang Liang, Jingyi Song, Yoon Seok Roh, Ekihiro Seki
BACKGROUND & AIMS: Toll-like receptor 4 (TLR4) signaling is activated through 2 adaptor proteins: MyD88 and TIR-domain containing adaptor-inducing interferon-β (TRIF). TLR4 and MyD88 are crucial in nonalcoholic steatohepatitis (NASH) and fibrosis. However, the role of TRIF in TLR4-mediated NASH and fibrosis has been elusive. This study investigated the differential roles of TRIF in hepatic steatosis and inflammation/fibrosis. METHODS: A choline-deficient amino acid defined (CDAA) diet was used for the mouse NASH model...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28455339/improved-%C3%AE-amylase-production-by-dephosphorylation-mutation-of-cred-an-arrestin-like-protein-required-for-glucose-induced-endocytosis-of-maltose-permease-and-carbon-catabolite-de-repression-in-aspergillus-oryzae
#19
Mizuki Tanaka, Tetsuya Hiramoto, Hinako Tada, Takahiro Shintani, Katsuya Gomi
Aspergillus oryzae produces copious amount of amylolytic enzymes, and MalP, a major maltose permease, is required for the expression of amylase-encoding genes. The expression of these genes is strongly repressed by carbon catabolite repression (CCR) in the presence of glucose. MalP is transported from the plasma membrane to the vacuole by endocytosis, which requires the HECT ubiquitin ligase HulA, an ortholog of yeast Rsp5. In yeast, arrestin-like proteins mediate endocytosis as adaptors of Rsp5 and transporters...
April 28, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28450223/gper-activation-is-effective-in-protecting-against-inflammation-induced-nigral-dopaminergic-loss-and-motor-function-impairment
#20
Julieta Mendes-Oliveira, Filipa Lopes Campos, Rita Alexandra Videira, Graça Baltazar
Increasing evidence suggest that excessive inflammatory responses from overactivated microglia play a critical role in Parkinson's disease (PD), contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent results from our group and others demonstrated that selective activation of G protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA neurons from 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether modulation of microglial responses is one of the mechanisms by which G1 exerts its DA neuroprotective effects...
April 24, 2017: Brain, Behavior, and Immunity
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