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https://www.readbyqxmd.com/read/29133239/emerging-role-of-plexins-signaling-in-glioma-progression-and-therapy
#1
Efthalia Angelopoulou, Christina Piperi
Gliomas are highly invasive brain tumors with increased resistance to chemotherapy and high recurrence rate. Neoplastic cells commonly infiltrate into the surrounding tissue even at low grade tumors. Cell migration is often ceased at white and grey matter junctions indicating the involvement of tropic and axon guidance molecules in glioma growth and invasion. Emerging evidence implicates plexin-semaphorin signaling in the pathobiology of gliomas. Plexins are transmembrane receptors divided into four subfamilies (Plexins-A to -D) with differential specificity and functionality...
November 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29113996/characterization-of-the-molecular-mechanisms-underlying-glucose-stimulated-insulin-secretion-from-isolated-pancreatic-%C3%AE-cells-using-ptmomics
#2
Taewook Kang, Pia Jensen, Honggang Huang, Gitte Lund Christensen, Nils Billestrup, Martin R Larsen
Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. However, the molecular mechanisms underlying the insulin secretion are unclear. Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins...
November 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29107805/neuronal-expression-patterns-of-the-plexina-family-during-zebrafish-development
#3
Sarah E Emerson, Sarah E Light, Alicia M Ebert
Plexins (Plxns) and Semaphorins (Semas) are key signaling molecules that regulate many aspects of development. Plxns are a family of transmembrane protein receptors that are activated upon extracellular binding by Semas. Activated Plxns trigger intracellular signaling cascades, which regulate a range of developmental processes, including axon guidance, neuronal positioning and vasculogenesis. Semas are a large family of both transmembrane and secreted signaling molecules, and show subtype specific binding to different Plxn family members...
October 28, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29100074/plexin-b2-mediates-physiologic-and-pathologic-functions-of-angiogenin
#4
Wenhao Yu, Kevin A Goncalves, Shuping Li, Hiroko Kishikawa, Guangjie Sun, Hailing Yang, Nil Vanli, Yunxia Wu, Yuxiang Jiang, Miaofen G Hu, Roland H Friedel, Guo-Fu Hu
Angiogenin (ANG) is a secreted ribonuclease (RNase) with cell-type- and context-specific roles in growth, survival, and regeneration. Although these functions require receptor-mediated endocytosis and appropriate subcellular localization, the identity of the cell surface receptor remains undefined. Here, we show that plexin-B2 (PLXNB2) is the functional receptor for ANG in endothelial, cancer, neuronal, and normal hematopoietic and leukemic stem and progenitor cells. Mechanistically, PLXNB2 mediates intracellular RNA processing that contribute to cell growth, survival, and regenerative capabilities of ANG...
November 2, 2017: Cell
https://www.readbyqxmd.com/read/29095088/vegf-a121a-binding-to-neuropilins-a-concept-revisited
#5
Sarvenaz Sarabipour, Feilim Mac Gabhann
All known splice isoforms of vascular endothelial growth factor A (VEGF-A) can bind to the receptor tyrosine kinases VEGFR-1 and VEGFR-2. We focus here on VEGF-A121a and VEGF-A165a, two of the most abundant VEGF-A splice isoforms in human tissue (1) , and their ability to bind the Neuropilin co-receptors NRP1 and NRP2. The Neuropilins are key vascular, immune, and nervous system receptors on endothelial cells, neuronal axons, and regulatory T cells respectively. They serve as co-receptors for the Plexins in Semaphorin binding on neuronal and vascular endothelial cells, and for the VEGFRs in VEGF binding on vascular and lymphatic endothelial cells, and thus regulate the initiation and coordination of cell signaling by Semaphorins and VEGFs...
November 2, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29091353/fyn-dependent-phosphorylation-of-plexina1-and-plexina2-at-conserved-tyrosines-is-essential-for-zebrafish-eye-development
#6
Riley M St Clair, Sarah E Emerson, Kristen P D'Elia, Marion E Weir, Anna M Schmoker, Alicia M Ebert, Bryan A Ballif
Plexins (Plxns) are semaphorin (Sema) receptors that play important signaling roles, particularly in the developing nervous system and vasculature. Sema-Plxn signaling regulates cellular processes such as cytoskeletal dynamics, proliferation, and differentiation. However, the receptor-proximal signaling mechanisms driving Sema-Plxn signal transduction are only partially understood. Plxn tyrosine phosphorylation is thought to play an important role in these signaling events as receptor and non-receptor tyrosine kinases have been shown to interact with Plxn receptors...
November 1, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29040270/analysis-of-the-interaction-of-plexin-b1-and-plexin-b2-with-rnd-family-proteins
#7
Thomas Wylie, Ritu Garg, Anne J Ridley, Maria R Conte
The Rnd family of proteins, Rnd1, Rnd2 and Rnd3, are atypical Rho family GTPases, which bind to but do not hydrolyse GTP. They interact with plexins, which are receptors for semaphorins, and are hypothesised to regulate plexin signalling. We recently showed that each Rnd protein has a distinct profile of interaction with three plexins, Plexin-B1, Plexin-B2 and Plexin-B3, in mammalian cells, although it is unclear which region(s) of these plexins contribute to this specificity. Here we characterise the binary interactions of the Rnd proteins with the Rho-binding domain (RBD) of Plexin-B1 and Plexin-B2 using biophysical approaches...
2017: PloS One
https://www.readbyqxmd.com/read/28973932/discovery-of-an-o-mannosylation-pathway-selectively-serving-cadherins-and-protocadherins
#8
Ida Signe Bohse Larsen, Yoshiki Narimatsu, Hiren Jitendra Joshi, Lina Siukstaite, Oliver J Harrison, Julia Brasch, Kerry M Goodman, Lars Hansen, Lawrence Shapiro, Barry Honig, Sergey Y Vakhrushev, Henrik Clausen, Adnan Halim
The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28953869/retrograde-semaphorin-plexin-signalling-drives-homeostatic-synaptic-plasticity
#9
Brian O Orr, Richard D Fetter, Graeme W Davis
Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis...
October 5, 2017: Nature
https://www.readbyqxmd.com/read/28948068/effect-of-food-intake-on-92-neurological-biomarkers-in-plasma
#10
Magnus Dencker, Ola Björgell, Joanna Hlebowicz
OBJECTIVE: This study evaluates the effect of food intake on 92 neurological biomarkers in plasma. Moreover, it investigated if any of the biomarkers were correlated with body mass index. MATERIALS AND METHODS: Twenty-two healthy subjects (11 male and 11 female aged 25.9 ± 4.2 years) were investigated. A total of 92 biomarkers were measured before a standardized meal as well as 30 and 120 min afterward with the Proseek Multiplex Neurology I kit. RESULTS: The levels for 13 biomarkers decreased significantly (p < ...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28927892/cd100-plexin-b2-promotes-the-inflammation-in-psoriasis-by-activating-nf-%C3%AE%C2%BAb-and-inflammasome-in-keratinocytes
#11
Chen Zhang, Chunying Xiao, Erle Dang, Jiao Cao, Zhenlai Zhu, Meng Fu, Xu Yao, Yufeng Liu, Boquan Jin, Gang Wang, Wei Li
Plexin-B2 (PlxnB2) and its ligand, CD100 (Semaphorin 4D), are originally identified as axon-guidance molecules that function during neuronal development; however, studies also showed that CD100-Plexins participate in various immune responses. In the present study, we found that the expression of PlxnB2 on keratinocytes was specifically increased in lesional skin of psoriasis patients, but not atopic dermatitis. Levels of soluble CD100 (sCD100) and membrane CD100 (mCD100) were elevated in sera of psoriasis patients and on keratinocytes of psoriatic skin, respectively...
September 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28912336/elevated-semaphorin-5a-in-patients-with-hashimoto-s-thyroiditis-a-case-control-study
#12
Yongping Liu, Shuo Wang, Qingling Guo, Yongze Li, Jing Qin, Na Zhao, Yushu Li, Zhongyan Shan, Weiping Teng
OBJECTIVE: Hashimoto's thyroiditis (HT) is characterized by elevated specific auto-antibodies, including TgAb and TPOAb. Increasing evidence has demonstrated the essential role of Th17 cells in HT. However, the underlying mechanism is still unclear. Semaphorin 5A (Sema 5A) is involved in several autoimmune diseases through the regulation of immune cells. The aim of the present study was to explore the role of Sema 5A in HT. METHODS: We measured serum Sema 5A levels in HT (n = 92) and healthy controls (n = 111) by enzyme-linked immunosorbent assay (ELISA)...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28902178/tumor-inhibitory-effect-of-ircr201-a-novel-cross-reactive-c-met-antibody-targeting-the-psi-domain
#13
Hyunkyu Park, Donggeon Kim, Eunmi Kim, Jason K Sa, Hee Won Lee, Suji Yu, Jiwon Oh, Seok-Hyung Kim, Yeup Yoon, Do-Hyun Nam
Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy. Based on its protumorigenic potentials, we developed IRCR201, a potent antagonistic antibody targeting the plexin-semaphorin-integrin (PSI) domain of c-Met, using synthetic human antibody phage libraries...
September 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28878126/endothelium-derived-extracellular-vesicles-promote-splenic-monocyte-mobilization-in-myocardial-infarction
#14
Naveed Akbar, Janet E Digby, Thomas J Cahill, Abhijeet N Tavare, Alastair L Corbin, Sushant Saluja, Sam Dawkins, Laurienne Edgar, Nadiia Rawlings, Klemen Ziberna, Eileen McNeill, Errin Johnson, Alaa A Aljabali, Rebecca A Dragovic, Mala Rohling, T Grant Belgard, Irina A Udalova, David R Greaves, Keith M Channon, Paul R Riley, Daniel C Anthony, Robin P Choudhury
Transcriptionally activated monocytes are recruited to the heart after acute myocardial infarction (AMI). After AMI in mice and humans, the number of extracellular vesicles (EVs) increased acutely. In humans, EV number correlated closely with the extent of myocardial injury. We hypothesized that EVs mediate splenic monocyte mobilization and program transcription following AMI. Some plasma EVs bear endothelial cell (EC) integrins, and both proinflammatory stimulation of ECs and AMI significantly increased VCAM-1-positive EV release...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28853092/involvement-of-semaphorin-sema4d-in-t-dependent-activation-of-b-cells
#15
Е М Kuklina, I V Nekrasova, Yu V Valieva
The involvement of endogenous semaphorin (Sema4D) into the key stage of T-dependent differentiation of B cells, formation of plasmoblasts, was demonstrated in vitro in T/B cell co-culture under conditions of polyclonal activation of T cells. The effect of semaphorin was not associated with activation of high-affinity Sema4D receptor plexin B1, but involves lowaffinity receptor CD72. These data indicate that Sema4D-dependent signal regulates not only the initial stage of B-cell activation, proliferative response to the antigen, but also further differentiation of B cells into plasma cells...
August 29, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28843905/role-of-neuropilin-2-in-the-immune-system
#16
REVIEW
S Schellenburg, A Schulz, D M Poitz, M H Muders
Neuropilins (NRPs) are single transmembrane receptors with short cytoplasmic tails and are dependent on receptors like VEGF receptors or Plexins for signal transduction. NRPs are known to be important in angiogenesis, lymphangiogenesis, and axon guidance. The Neuropilin-family consists of two members, Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). They are up to 44 % homologous and conserved in all vertebrates. High levels of NRP2 are found on immune cells. Current research is very limited regarding the functions of NRP2 on these cells...
October 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28835374/low-affinity-binding-in-cis-to-p2y2r-mediates-force-dependent-integrin-activation-during-hantavirus-infection
#17
Virginie Bondu, Chenyu Wu, Wenpeng Cao, Peter C Simons, Jennifer Gillette, Jieqing Zhu, Laurie Erb, X Frank Zhang, Tione Buranda
Pathogenic hantaviruses bind to the plexin-semaphorin-integrin (PSI) domain of inactive, β3 integrins. Previous studies have implicated a cognate cis interaction between the bent conformation β5/β3 integrins and an arginine-glycine-aspartic acid (RGD) sequence in the first extracellular loop of P2Y2R. With single-molecule atomic force microscopy, we show a specific interaction between an atomic force microscopy tip decorated with recombinant αIIbβ3 integrins and (RGD)P2Y2R expressed on cell membranes. Mutation of the RGD sequence to RGE in the P2Y2R removes this interaction...
October 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28817310/semaphorins-and-their-roles-in-airway-biology-potential-as-therapeutic-targets
#18
Hesam Movassagh, Forough Khadem, Abdelilah S Gounni
Semaphorins are a large family of proteins originally identified as axon guidance cues which play a crucial role in neural development. They are also ubiquitously expressed beyond the nervous system and contribute to regulation of essential cell functions such as cell migration, proliferation, and adhesion. Binding of semaphorins to their receptors, including plexins and neuropilins, triggers diverse signaling pathways which are involved in the pathogenesis of various diseases from cancer to autoimmune and allergic disorders...
August 17, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28792859/elucidating-the-role-of-plexin-d1-in-body-fat-distribution-and-susceptibility-to-metabolic-disease-using-a-zebrafish-model-system
#19
James E N Minchin, John F Rawls
Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes and cancer were responsible for 68% of all deaths worldwide in 2012. The regional distribution of lipid deposited within adipose tissue (AT) - so called body fat distribution (BFD) - is a strong risk factor for NCDs. BFD is highly heritable; however, the genetic basis of BFD is almost entirely unknown. Genome-wide association studies have identified several loci associated with BFD, including at Plexin D1 (PLXND1) - a gene known to modulate angiogenesis...
July 27, 2017: Adipocyte
https://www.readbyqxmd.com/read/28765893/endothelial-semaphorin-7a-promotes-seawater-aspiration-induced-acute-lung-injury-through-plexin-c1-and-%C3%AE-1-integrin
#20
Minlong Zhang, Xue Yan, Wei Liu, Ruilin Sun, Yonghong Xie, Faguang Jin
Inflammation and edema are two main characteristics in seawater aspiration‑induced acute lung injury (ALI). In a previous study of the authors, it was demonstrated that endothelial semaphorin 7A (SEMA7A) serves an important role in the development of seawater‑induced inflammation and edema. However, the mechanism of endothelial SEMA7A‑mediated ALI remains unclear. Therefore, the authors explored the effect of SEMA7A in rat pulmonary microvascular endothelial cells (RPMVECs) and the interaction between endothelial SEMA7A and alveolar macrophages during seawater aspiration‑induced ALI...
October 2017: Molecular Medicine Reports
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