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https://www.readbyqxmd.com/read/28052247/sema-1a-reverse-signaling-promotes-midline-crossing-in-response-to-secreted-semaphorins
#1
Melissa Hernandez-Fleming, Ethan W Rohrbach, Greg J Bashaw
Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28038319/recruitment-of-tiam1-to-semaphorin-4d-activates-rac-and-enhances-proliferation-invasion-and-metastasis-in-oral-squamous-cell-carcinoma
#2
Hua Zhou, Maricel G Kann, Emily K Mallory, Ying-Hua Yang, Amr Bugshan, Nada O Binmadi, John R Basile
The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth...
December 27, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28027822/semaphorin-4d-enhances-angiogenic-potential-and-suppresses-osteo-odontogenic-differentiation-of-human-dental-pulp-stem-cells
#3
Ting Zou, Waruna Lakmal Dissanayaka, Shan Jiang, Shuai Wang, Boon Chin Heng, Xiaojing Huang, Chengfei Zhang
INTRODUCTION: To investigate the roles of semaphorin 4D (Sema4D)/plexin-B1 signaling on the angiogenic potential and osteo-/odontogenic differentiation of human dental pulp stem cells (DPSCs) and to uncover the corresponding molecular mechanisms. METHODS: DPSCs were treated with Sema4D (10 μg/mL) for different time durations. Osteo-/odontogenic differentiation was assessed by quantifying alkaline phosphatase activity, mineralized nodule formation, and osteo-/odontogenic gene (ALP, Col1A1, BSP, RUNX2, and DSPP) and protein (Col1A1 and DSPP) expression...
December 24, 2016: Journal of Endodontics
https://www.readbyqxmd.com/read/28007914/a-reverse-signaling-pathway-downstream-of-sema4a-controls-cell-migration-via-scrib
#4
Tianliang Sun, Lida Yang, Harmandeep Kaur, Jenny Pestel, Mario Looso, Hendrik Nolte, Cornelius Krasel, Daniel Heil, Ramesh K Krishnan, Marie-Josée Santoni, Jean-Paul Borg, Moritz Bünemann, Stefan Offermanns, Jakub M Swiercz, Thomas Worzfeld
Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28004109/identification-of-tmprss2-erg-mechanisms-in-prostate-cancer-invasiveness-involvement-of-mmp-9-and-plexin-b1
#5
Bide Liu, Xiao Gu, Tianbao Huang, Yang Luan, Xuefei Ding
The relationship of TMPRSS2-ERG fusion gene with matrix metalloproteinase-9 (MMP-9) and PLXNB1 (plexin B1) in regulation of prostate cancer (PCa) aggressiveness was investigated. Fluorescence in situ hybridization (FISH) assays, qRT-PCR and western blot analysis were employed to detect the expression of TMPRSS2-ERG fusion gene, ERG, MMP-9 and PLXNB1 of 135 human tissues, which included 55 metastatic PCa cases, 50 localized PCa cases and 30 BPH cases. Then using siRNA (anti-ERG, MMP-9 and PLXNB1, respectively) downregulation of the target gene of VCaP and PC-3 cells, MTT and Transwell were performed...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/28003812/semaphorin-4c-a-novel-component-of-b-cell-polarization-in-th2-driven-immune-responses
#6
Di Xue, Marylin Desjardins, Gabriel N Kaufman, Marianne Béland, Salem Al-Tememi, Eisha Ahmed, Shao Tao, Roland H Friedel, Walid Mourad, Bruce D Mazer
BACKGROUND: Semaphorins are important molecules in embryonic development and multiple semaphorins have been identified as having key roles in immune regulation. To date, there is little known about Semaphorin 4C (Sema4C) in immune biology. We report for the first time that Sema4C is inducible in human and murine B-cells and may be important for normal B-cell development. METHODS: Human tonsillar B-cells were studied following activation via anti-CD40 antibodies in the presence or absence of representative Th1, Th2, and regulatory cytokines...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27984026/allosteric-inhibition-of-a-semaphorin-4d-receptor-plexin-b1-by-a-high-affinity-macrocyclic-peptide
#7
Yukiko Matsunaga, Nasir K Bashiruddin, Yu Kitago, Junichi Takagi, Hiroaki Suga
Semaphorin axonal guidance factors are multifunctional proteins that play important roles in immune response, cancer cell proliferation, and organogenesis, making semaphorins and their signaling receptor plexins important drug targets for various diseases. However, the large and flat binding surface of the semaphorin-plexin interaction interface is difficult to target by traditional small-molecule drugs. Here, we report the discovery of a high-affinity plexin B1 (PlxnB1)-binding macrocyclic peptide, PB1m6 (KD = 3...
November 17, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27912840/the-semaphorins-and-their-receptors-as-modulators-of-tumor-progression
#8
Gera Neufeld, Yelena Mumblat, Tanya Smolkin, Shira Toledano, Inbal Nir-Zvi, Keren Ziv, Ofra Kessler
The semaphorins were initially characterized as repulsive axon guidance factors. However, they are currently also recognized as important regulators of diverse biological processes which include regulation of immune responses, angiogenesis, organogenesis, and a variety of additional physiological and developmental functions. The semaphorin family consists of more than 20 genes divided into seven subfamilies, all of which contain the sema domain signature. They usually transduce signals by activation of receptors belonging to the plexin family, either directly, or indirectly following the binding of some semaphorins to receptors of the neuropilin family which subsequently associate with plexins...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27906605/current-drug-design-to-target-the-semaphorin-neuropilin-plexin-complexes
#9
Lionel A T Meyer, Justine Fritz, Marie Pierdant-Mancera, Dominique Bagnard
The Semaphorin/Neuropilin/Plexin (SNP) complexes control a wide range of biological processes. Consistently, activity deregulation of these complexes is associated with many diseases. The increasing knowledge on SNP had in turn validated these molecular complexes as novel therapeutic targets. Targeting SNP activities by small molecules, antibodies and peptides or by soluble semaphorins have been proposed as new therapeutic approach. This review is focusing on the latest demonstration of this potential and discusses some of the key questions that need to be addressed before translating SNP targeting into clinically relevant approaches...
November 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27895757/expression-of-semaphorin-6d-and-its-receptor-plexin-a1-in-gastric-cancer-and-their-association-with-tumor-angiogenesis
#10
Yanjie Lu, Qian Xu, Lei Chen, Yanzhen Zuo, Shaochen Liu, Yatao Hu, Xiaoru Li, Yuhong Li, Xiangyang Zhao
The semaphorin and plexin family of ligands and receptor proteins provides important axon growth and guidance cues required for development. In recent years, studies have expanded their role in the regulation of cardiac morphogenesis and tumorigenesis. However, the mechanism responsible for their role in regulating cancer development and progression has not been clarified. In the present study, semaphorin 6D (Sema6D) and its receptor plexin-A1 were identified to be expressed at high levels in vascular epithelial cells within gastric cancer, and were positively correlated with vascular endothelial growth factor receptor 2 (VEGFR2)...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27871341/functional-analysis-of-a-nf-%C3%AE%C2%BAb-transcription-factor-in-the-immune-defense-of-oriental-fruit-fly-bactrocera-dorsalis-hendel-diptera-tephritidae
#11
Z Shi, H Liang, Y Hou
Although some novel antimicrobial peptides (AMP) have been successfully isolated from Bactrocera dorsalis Hendel, the mechanisms underlying the induction of these peptides are still elusive. The homolog of NF-κB transcription factor Relish, designated as BdRelish, was cloned from B. dorsalis. The full length cDNA of BdRelish is 3954 bp with an open reading frame that encodes 1013 amino acids. Similar to Drosophila Relish and the mammalian p100, it is a compound protein containing a conserved Rel homology domain, an IPT (Ig-like, plexins, transcription factors) domain and an IκB-like domain (four ankyrin repeats), the nuclear localization signal RKRRR is also detected at the residues 449-453, suggesting that it has homology to Relish and it is a member of the Rel family of transcription activator proteins...
November 22, 2016: Bulletin of Entomological Research
https://www.readbyqxmd.com/read/27856318/sympathetic-nerve-repulsion-inhibited-by-designer-molecules-in-vitro-and-role-in-experimental-arthritis
#12
Julia Kunath, Nicolas Delaroque, Michael Szardenings, Ines Neundorf, Rainer H Straub
AIMS: In rheumatoid arthritis and collagen type II arthritis (CIA), sympathetic nerve fibers get lost in inflamed tissue. The process is probably induced by nerve repellent factors like semaphorin 3F (SEMA3F). Repulsion of sympathetic nerve fibers in inflamed tissue has proinflammatory effects due to the loss of anti-inflammatory neurotransmitters. We hypothesized that design molecules like antibodies and specific peptides that inhibit nerve fiber repulsion can ameliorate CIA. MATERIALS AND METHODS: Two blocking antibodies were used and four blocking peptides were generated using the phage display technique with the targets of SEMA3F and plexin-A2...
January 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27812179/protein-o-mannosylation-in-the-murine-brain-occurrence-of-mono-o-mannosyl-glycans-and-identification-of-new-substrates
#13
Markus F Bartels, Patrick R Winterhalter, Jin Yu, Yan Liu, Mark Lommel, Frank Möhrlen, Huaiyu Hu, Ten Feizi, Ulrika Westerlind, Thomas Ruppert, Sabine Strahl
Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated...
2016: PloS One
https://www.readbyqxmd.com/read/27803667/wedelolactone-enhances-osteoblastogenesis-but-inhibits-osteoclastogenesis-through-sema3a-nrp1-plexina1-pathway
#14
Yan-Qiu Liu, Xiao-Fei Han, Jun-Xia Bo, Hui-Peng Ma
Bone remodeling balance is maintained by tight coupling of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Thus, agents with the capacity to regulate osteoblastogenesis and osteoclastogenesis have been investigated for therapy of bone-related diseases such as osteoporosis. In this study, we found that wedelolactone, a compound isolated from Ecliptae herba, and a 9-day incubation fraction of conditioned media obtained from wedelolactone-treated bone marrow mesenchymal stem cell (BMSC) significantly inhibited tartrate-resistant acid phosphatase (TRAP) activity in RANKL-stimulated osteoclastic RAW264...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27798666/a-novel-physiological-glycosaminoglycan-deficient-splice-variant-of-neuropilin-1-is-anti-tumorigenic-in-vitro-and-in-vivo
#15
Céline Hendricks, Johanne Dubail, Laura Brohée, Yves Delforge, Alain Colige, Christophe Deroanne
Neuropilin-1 (NRP1) is a transmembrane protein acting as a co-receptor for several growth factors and interacting with other proteins such as integrins and plexins/semaphorins. It is involved in axonal development, angiogenesis and cancer progression. Its primary mRNA is subjected to alternative splicing mechanisms generating different isoforms, some of which lack the transmembrane domain and display antagonist properties to NRP1 full size (FS). NRP1 is further post-translationally modified by the addition of glycosaminoglycans (GAG) side chains through an O-glycosylation site at serine612...
2016: PloS One
https://www.readbyqxmd.com/read/27791111/foxo6-affects-plxna4-mediated-neuronal-migration-during-mouse-cortical-development
#16
Ricardo H Paap, Saskia Oosterbroek, Cindy M R J Wagemans, Lars von Oerthel, Raymond D Schellevis, Annemarie J A Vastenhouw-van der Linden, Marian J A Groot Koerkamp, Marco F M Hoekman, Marten P Smidt
The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6(+/-) and FoxO6(-/-) mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of FoxO6 We then show that FoxO6 binds to DAF-16-binding elements in the Plexin A4 (Plxna4) promoter region and affects Plxna4 expression...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27787872/characterizing-semaphorin-signaling-in-vivo-using-c-elegans
#17
Akira Nukazuka, Shin Takagi
A small model animal Caenorhabditis elegans is particularly suitable for genetic analysis, but cell-type-specific biochemistry is a formidable task in this organism. Here we describe techniques utilizing transgenic C. elegans strains expressing epitope-tagged proteins for analyzing biochemical events, such as protein phosphorylation and formation of protein complex, in a small number of a specific group of cells at a defined stage of development. The techniques are useful for elucidating that C. elegans semaphorin-plexin signaling systems regulate epidermal morphogenesis through modulating TOR signaling and its downstream targets...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27787869/characterization-of-the-effects-of-semaphorin-4d-signaling-on-angiogenesis
#18
Hua Zhou, Ying-Hua Yang, John R Basile
The semaphorins and plexins comprise a family of cysteine-rich cell surface and secreted proteins originally shown to control nerve growth and the immune response, but that have recently been implicated in a wide variety of developmental and pathological processes that are influenced by cell adhesion and migration. Along those lines, our group and others have found that Semaphorin 4D (SEMA4D) plays an important role in angiogenesis by promoting chemotaxis of endothelial cells, which express its receptor, Plexin-B1...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27787852/an-electrical-impedance-based-method-for-quantitative-real-time-analysis-of-semaphorin-elicited-endothelial-cell-collapse
#19
Chiara Camillo, Noemi Gioelli, Federico Bussolino, Guido Serini
Semaphorins (SEMA) are chemorepulsive guidance cues that, acting through plexin receptors, inhibit integrin-mediated cell adhesion to the extracellular matrix. The ensuing cell retraction and collapse is a key biological event downstream of SEMA/plexin signaling that is however hard to precisely quantify. Here, we describe a quantitative approach that allows monitoring over time the evolution of SEMA3E/plexin D1-elicited endothelial cell collapse. This method exploits the xCELLigence platform, an electrical impedance-based system in which microelectronic sensor arrays are integrated into the bottom of microplate wells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27787849/using-heterologous-cos-7-cells-to-identify-semaphorin-signaling-components
#20
Atsuko Sakurai, Colleen L Doçi, J Silvio Gutkind
Semaphorins are a family of membrane-bound and secreted type of proteins which were initially identified as chemorepulsive axon guidance molecules. Plexins and neuropilins are two major receptor families of semaphorins, and their common downstream targets are the actin cytoskeleton and cell-to-extracellular matrix adhesions. Semaphorins promote the collapse of growth cones by inducing rapid changes in the cytoskeleton and disassembly of focal adhesion structures. When transfected with appropriate receptors, non-neuronal COS-7 cells exhibit a similar cell collapse phenotype upon semaphorin stimulation...
2017: Methods in Molecular Biology
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