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In vivo protein protein interaction

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https://www.readbyqxmd.com/read/28645175/perturbation-to-cholesterol-at-the-neuromuscular-junction-confers-botulinum-neurotoxin-a-sensitivity-to-neonatal-mice
#1
Baskaran Thyagarajan, Joseph G Potian, Joseph J McArdle, Padmamalini Baskaran
Botulinum neurotoxin A (BoNT/A) cleaves SNAP25 at the motor nerve terminals (MNT) and inhibits stimulus evoked acetylcholine release (SEAR). This causes skeletal muscle paralysis. However, younger neonatal mice (<P7; less than 7 days old) are resistant to the neuroparalytic effects of BoNT/A. That is, in vivo injection of BoNT/A at the innervations of Extensor digitorum longus (EDL) muscle in the hindlimbs inhibited the toe spread reflex within 24 hours following BoNT/A injection in adult mouse and in older (> P7) neonatal mice younger than 7 days-age remained unaffected by BoNT/A injection...
June 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28645103/colxv-promotes-adipocyte-differentiation-via-inhibiting-dna-methylation-and-camp-pka-pathway-in-mice
#2
Guannv Liu, Meihang Li, Yatao Xu, Song Wu, Muhammad Saeed, Chao Sun
Extracellular matrix (ECM), as an essential component of adipose tissue, not only provides mechanical support for adipocyte growth, but also participates in ECM-adipocyte communication via various secreted proteins, including highly enriched collagens. Collagen XV (ColXV) is a secreted non-fibrillar collagen within ECM Basement Membrane (BM) zones and well recognized as a tumor suppressor. However, the role of ColXV in adipose tissue is still unknown. In this study, high fat diet (HFD) fed mice were used as obese model, in which we deeply investigated the interaction between ColXV and adipocyte differentiation or adipose metabolism...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642882/tumor-related-exosomes-contribute-to-tumor-promoting-microenvironment-an-immunological-perspective
#3
REVIEW
Wuzhen Chen, Jingxin Jiang, Wenjie Xia, Jian Huang
Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-β...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28642865/spinal-muscular-atrophy-from-defective-chaperoning-of-snrnp-assembly-to-neuromuscular-dysfunction
#4
REVIEW
Maia Lanfranco, Neville Vassallo, Ruben J Cauchi
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN) protein. SMN is part of a multiprotein complex that also includes Gemins 2-8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5) complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs) to generate small nuclear ribonucleoproteins (snRNPs), which are the operating components of the spliceosome...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28642747/propionibacterium-freudenreichii-surface-protein-slpb-is-involved-in-adhesion-to-intestinal-ht-29-cells
#5
Fillipe L R do Carmo, Houem Rabah, Song Huang, Floriane Gaucher, Martine Deplanche, Stéphanie Dutertre, Julien Jardin, Yves Le Loir, Vasco Azevedo, Gwénaël Jan
Propionibacterium freudenreichii is a beneficial bacterium traditionally used as a cheese ripening starter and more recently for its probiotic abilities based on the release of beneficial metabolites. In addition to these metabolites (short-chain fatty acids, vitamins, and bifidogenic factor), P. freudenreichii revealed an immunomodulatory effect confirmed in vivo by the ability to protect mice from induced acute colitis. This effect is, however, highly strain-dependent. Local action of metabolites and of immunomodulatory molecules is favored by the ability of probiotics to adhere to the host cells...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28642367/the-activities-of-the-c-terminal-regions-of-the-formin-protein-disheveled-associated-activator-of-morphogenesis-daam-in-actin-dynamics
#6
Andrea Teréz Vig, István Földi, Szilárd Szikora, Ede Migh, Rita Gombos, Mónika Ágnes Tóth, Tamás Huber, Réka Pintér, Gábor Csaba Talián, József Mihály, Beáta Bugyi
Disheveled-associated activator of morphogenesis (DAAM) is a diaphanous-related formin protein essential for the regulation of actin cytoskeleton dynamics in diverse biological processes. The conserved formin homology 1 and 2 (FH1-FH2) domains of DAAM catalyze actin nucleation and processively mediate filament elongation. These activities are indirectly regulated by the N-, and C-terminal regions flanking the FH1-FH2 domains. Recently, the C-terminal diaphanous-autoregulatory domain (DAD) and the C-terminus (CT) of formins have also been shown to regulate actin assembly by directly interacting with actin...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642366/saccharomyces-cerevisiae-red1-protein-exhibits-nonhomologous-dna-end-joining-activity-and-potentiates-hop1-promoted-pairing-of-double-stranded-dna
#7
Rucha Kshirsagar, Indrajeet Ghodke, Kalappa Muniyappa
Elucidation of the function of synaptonemal complex (SC) in <Saccharomyces cerevisiae> has mainly focused on in vivo analysis of recombination-defective meiotic mutants. Consequently, significant gaps remain in the mechanistic understanding of the activities of different SC proteins and the functional relationships among them. S. cerevisiae Hop1 and Red1 are essential structural components of the SC axial/lateral elements. Previous studies have demonstrated that Hop1 is a structure-specific DNA-binding protein that exhibits high affinity for the Holliday junction, promotes DNA bridging, condensation and pairing between duplex DNA molecules...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642245/a-reporter-mouse-model-for-in-vivo-tracing-and-in-vitro-molecular-studies-of-melanocytic-lineage-cells-and-their-diseases
#8
Melissa Crawford, Valerie Leclerc, Lina Dagnino
Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, as well as melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations...
June 22, 2017: Biology Open
https://www.readbyqxmd.com/read/28642045/mutations-on-ftsz-lateral-helix-h3-that-disrupt-cell-viability-hamper-reorganization-of-polymers-on-lipid-surfaces
#9
Ileana F Márquez, Pablo Mateos-Gil, Jae Yen Shin, Rosalba Lagosb, Octavio Monasterio, Marisela Vélez
FtsZ filaments localize at the middle of the bacterial cell and participate in the formation of a contractile ring responsible for cell division. Previous studies demonstrated that the highly conserved negative charge of glutamate 83 and the positive charge of arginine 85 located in the lateral helix H3 bend of Escherichia coli FtsZ are required for in vivo cell division. In order to understand how these lateral mutations impair the formation of a contractile ring, we extend previous in vitro characterization of these mutants in solution to study their behavior on lipid modified surfaces...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641528/drug-design-synthesis-and-in-vitro-evaluation-of-substituted-benzofurans-as-hsp90-inhibitors
#10
Sundeep Kadasi, Thadeu E M M Costa, Neha Arukala, Mallika Toshakani, Chaitanya Duggineti, Sreekanth Thota, Sayan Dutta Gupta, Shiva Raj, Carmen Penido, Maria G Henriques, Nulgumnalli Manjunathaiah Raghavendra
BACKGROUND: Heat shock protein 90 is a molecular chaperone required for the stability and function of several client proteins that promote cancer cell growth and/or survival. Discovery of Hsp90 inhibitors has emerged as an attractive target of research in cancer therapeutics. Natural products like geldanamycin and radicicol are established Hsp90 inhibitors, but face limitations with toxicity and inactivity, by in vivo studies respectively. However, they lay the logical starting point for the design of novel synthetic or semi-synthetic congeners as Hsp90 inhibitors...
June 22, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28641111/structural-insights-into-modulation-of-neurexin-neuroligin-trans-synaptic-adhesion-by-mdga1-neuroligin-2-complex
#11
Jung A Kim, Doyoun Kim, Seoung Youn Won, Kyung Ah Han, Dongseok Park, Eunju Cho, Nayoung Yun, Hyun Joo An, Ji Won Um, Eunjoon Kim, Jie-Oh Lee, Jaewon Ko, Ho Min Kim
Membrane-associated mucin domain-containing glycosylphosphatidylinositol anchor proteins (MDGAs) bind directly to neuroligin-1 (NL1) and neuroligin-2 (NL2), thereby respectively regulating excitatory and inhibitory synapse development. However, the mechanisms by which MDGAs modulate NL activity to specify development of the two synapse types remain unclear. Here, we determined the crystal structures of human NL2/MDGA1 Ig1-3 complex, revealing their stable 2:2 arrangement with three interaction interfaces. Cell-based assays using structure-guided, site-directed MDGA1 mutants showed that all three contact patches were required for the MDGA's negative regulation of NL2-mediated synaptogenic activity...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#12
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28640668/absence-of-the-fragile-x-mental-retardation-protein-results-in-defects-of-rna-editing-of-neuronal-mrnas-in-mouse
#13
Alice Filippini, Daniela Bonini, Caroline Lacoux, Laura Pacini, Maria Zingariello, Laura Sancillo, Daniela Bosisio, Valentina Salvi, Jessica Mingardi, Luca La Via, Francesca Zalfa, Claudia Bagni, Alessandro Barbon
The fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to the absence of FMRP, a protein regulating RNA metabolism. Recently, an unexpected function of FMRP in modulating the activity of Adenosine Deaminase Acting on RNA (ADAR) enzymes has been reported both in Drosophila and Zebrafish. ADARs are RNA-binding proteins that increase transcriptional complexity through a post-transcriptional mechanism called RNA editing. In order to evaluate the ADAR2-FMRP interaction in mammals we analysed several RNA editing re-coding sites in the fmr1 knockout (KO) mice...
June 22, 2017: RNA Biology
https://www.readbyqxmd.com/read/28640580/a-bio-inspired-alginate-gum-arabic-hydrogel-with-micro-nano-scale-structures-for-controlled-drug-release-in-chronic-wound-healing
#14
Mi Li, Haichang Li, Xiangguang Li, Hua Zhu, Zihui Xu, Lianqing Liu, Jianjie Ma, Mingjun Zhang
Bio-polymeric hydrogels have drawn increasingly research interests in biomaterials due to its tunable physical and chemical properties for both creating bioactive cellular micro-environment and serving as sustainable therapeutic reagents. Inspired by a naturally occurring hydrogel secreted from the carnivorous Sundew plant for trapping insects, here we have developed a bio-inspired hydrogel to deliver mitsugumin53 (MG53), an important protein in cell membrane repair, for chronic wound healing. Both chemical compositions and micro/nano morphological properties inherent from the natural Sundew hydrogel were mimicked using sodium alginate and gum arabic with calcium ion-mediated cross-linking...
June 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28638591/replicable-in-vivo-physiological-and-behavioral-phenotypes-of-the-shank3b-null-mutant-mouse-model-of-autism
#15
Sameer C Dhamne, Jill L Silverman, Chloe E Super, Stephen H T Lammers, Mustafa Q Hameed, Meera E Modi, Nycole A Copping, Michael C Pride, Daniel G Smith, Alexander Rotenberg, Jacqueline N Crawley, Mustafa Sahin
BACKGROUND: Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28637841/protein-tyrosine-phosphatase-%C3%AE-mediates-the-sema3a-induced-cortical-basal-dendritic-arborization-through-the-activation-of-fyn-tyrosine-kinase
#16
Fumio Nakamura, Takako Okada, Maria Shishikura, Noriko Uetani, Masahiko Taniguchi, Takeshi Yagi, Yoichiro Iwakura, Toshio Ohshima, Yoshio Goshima, Stephen M Strittmatter
Leukocyte common antigen related (LAR) class protein tyrosine phosphatases (PTPs) are critical for axonal guidance; however, their relation to specific guidance cues is poorly defined. We here show that PTP-3, LAR homologue in C. elegans, is involved in axon guidance regulated by Sema2A-signaling. PTPδ, one of vertebrate LAR class PTPs, participates in Sema3A-induced growth cone collapse response of primary cultured dorsal root ganglion neurons from M. musculus embryos. In vivo, however, the contribution of PTPδ in Sema3A-regualted axon guidance was minimal...
June 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28637784/tnfr2-stimulation-promotes-mitochondrial-fusion-via-stat3-and-nf-kb-dependent-activation-of-opa1-expression
#17
Jinliang Nan, Hengxun Hu, Yong Sun, Lianlian Zhu, Yingchao Wang, Zhiwei Zhong, Jing Zhao, Na Zhang, Ya Wang, Yaping Wang, Jian Ye, Ling Zhang, Xinyang Hu, Wei Zhu, Jian'an Wang
Rationale: Mitochondria are important cellular organelles and play essential roles in maintaining cell structure and function. Emerging evidence indicates that in addition to having pro-inflammatory and pro-apoptotic effects, tumor necrosis factor α (TNFα) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFα receptor 2 (TNFR2). Objective: The present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28637754/functional-evolution-of-influenza-ns1-protein-in-currently-circulating-human-2009-pandemic-h1n1-viruses
#18
Amelia M Clark, Aitor Nogales, Luis Martinez-Sobrido, David J Topham, Marta L DeDiego
In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist, but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here, we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637751/ifit2-is-a-restriction-factor-in-rabies-virus-pathogenicity
#19
Benjamin M Davis, Volker Fensterl, Tessa M Lawrence, Andrew W Hudacek, Ganes C Sen, Matthias J Schnell
Understanding the interactions between rabies virus (RABV) and individual host cell proteins is critical for the development of targeted therapies. Here we report that Interferon-induced protein with tetratricopeptide repeats 2 (Ifit2), an interferon-stimulated gene (ISG) with possible RNA-binding capacity, is an important restriction factor for rabies virus. When Ifit2 was depleted, RABV grew more quickly in mouse neuroblastoma in vitro This effect was replicated in vivo, where Ifit2 knockout mice displayed a dramatically more severe disease phenotype than wild-type after intranasal inoculation of RABV...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637687/inhibition-of-cdk4-6-by-palbociclib-significantly-extends-survival-in-medulloblastoma-patient-derived-xenograft-mouse-models
#20
Michelle L Cook Sangar, Laura A Genovesi, Madison W Nakamoto, Melissa J Davis, Sue E Knoblaugh, Pengxiang Ji, Amanda Millar, Brandon Wainwright, James M Olson
  <p>Bioinformatics analysis followed by in vivo studies in patient-derived xenograft models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly Group 3 MYC-amplified tumors which have the worst clinical prognosis.</p> <br />Experimental Design: <p>A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets.  The top hit from this analysis was validated in vivo using patient-derived xenograft models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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