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https://www.readbyqxmd.com/read/29154130/neuropilin-2-plexina3-receptors-associate-with-glua1-and-mediate-sema3f-dependent-homeostatic-scaling-in-cortical-neurons
#1
Qiang Wang, Shu-Ling Chiu, Eleftheria Koropouli, Ingie Hong, Sarah Mitchell, Teresa P Easwaran, Natalie R Hamilton, Ahleah S Gustina, Qianwen Zhu, David D Ginty, Richard L Huganir, Alex L Kolodkin
Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor mediate homeostatic plasticity in cortical neurons. Sema3F-Npn-2/PlexA3 signaling is essential for cell surface AMPAR homeostatic downscaling in response to an increase in neuronal activity, Npn-2 associates with AMPARs, and Sema3F regulates this interaction...
November 14, 2017: Neuron
https://www.readbyqxmd.com/read/29141914/proteotranscriptomics-reveal-signaling-networks-in-the-ovarian-cancer-microenvironment
#2
Thomas Worzfeld, Florian Finkernagel, Silke Reinartz, Anne Konzer, Till Adhikary, Andrea Nist, Thorsten Stiewe, Uwe Wagner, Mario Looso, Johannes Graumann, Rolf Müller
Ovarian cancer is characterized by early transcoelomic metastatic spread via the peritoneal fluid, where tumor cell spheroids (TU), tumor-associated T cells (TAT), and macrophages (TAM) create a unique microenvironment promoting cancer progression, chemoresistance and immuno-suppression. However, the underlying signaling mechanisms remain largely obscure.  To chart these signaling networks, we performed comprehensive proteomic and transcriptomic analyses of TU, TAT and TAM from ascites of ovarian cancer patients...
November 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29138447/the-semaphorin-3a-inhibitor-sm-345431-preserves-corneal-nerve-and-epithelial-integrity-in-a-murine-dry-eye-model
#3
Risa Yamazaki, Katsuya Yamazoe, Satoru Yoshida, Shin Hatou, Emi Inagaki, Hideyuki Okano, Kazuo Tsubota, Shigeto Shimmura
Dry eye disease (DED) is a common disorder causing discomfort and ocular fatigue. Corneal nerves are compromised in DED, which may further cause loss of corneal sensation and decreased tear secretion. Semaphorin 3A (Sema3A) is expressed by the corneal epithelium under stress, and is known as an inhibitor of axonal regeneration. Using a murine dry eye model, we found that topical SM-345431, a selective Sema3A inhibitor, preserved corneal sensitivity (2.3 ± 0.3 mm versus 1.4 ± 0.1 mm in vehicle control, p = 0...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133239/emerging-role-of-plexins-signaling-in-glioma-progression-and-therapy
#4
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
#5
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/29113226/silencing-of-semaphorin-3c-suppresses-cell-proliferation-and-migration-in-mcf-7-breast-cancer-cells
#6
Xiaofang Zhu, Xiangjian Zhang, Zhiqiang Ye, Yizuo Chen, Lin Lv, Xiaohua Zhang, Hongye Hu
Previous studies have suggested that semaphorin 3C (SEMA3C) is involved in the tumorigenesis and metastasis of a number of types of cancer. The aim of the present study was to investigate the role of SEMA3C in the proliferation and migration of MCF-7 breast cancer cells. Small interfering (si)RNA sequences targeting SEMA3C were constructed and transfected into MCF-7 cells in order to silence the expression of SEMA3C. Cell proliferation and migration were measured using CCK-8 and Transwell assays, respectively...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113093/view-point-semaphorin-3e-an-emerging-modulator-of-natural-killer-cell-functions
#7
REVIEW
Abdulaziz Alamri, Abdelilah Soussi Gounni, Sam K P Kung
Semaphorin-3E (Sema-3E) is a member of a large family of proteins originally identified as axon guidance cues in neural development. It is expressed in different cell types, such as immune cells, cancer cells, neural cells, and epithelial cells. Subsequently, dys-regulation of Sema-3E expression has been reported in various biological processes that range from cancers to autoimmune and allergic diseases. Recent work in our laboratories revealed a critical immunoregulatory role of Sema-3E in experimental allergic asthma...
November 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29111592/inflammatory-milieu-cultivated-sema3a-signaling-promotes-chondrocyte-apoptosis-in-knee-osteoarthritis
#8
Jie Sun, Xuelei Wei, Zengliang Wang, Yunjiao Liu, Jie Lu, Yandong Lu, Meng Cui, Xi Zhang, Fangguo Li
Osteoarthritis (OA) is the leading degenerative joint disease and featured by articular cartilage destruction, where chondrocyte apoptosis plays a critical role. Semaphorin-3A (Sema3A) has been implicated in OA chondrocyte physiology. In this study we aimed to uncover how Sema3A signaling is regulated in chondrocytes and investigate its role in OA chondrocyte survival. Here, we report that Sema3A and its receptor neuropilin-1 (Nrp1) are synchronously upregulated in cartilage chondrocytes of knee OA patients...
November 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29107805/neuronal-expression-patterns-of-the-plexina-family-during-zebrafish-development
#9
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/29095088/vegf-a121a-binding-to-neuropilins-a-concept-revisited
#10
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
#11
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/29082313/myeloid-cell-neuropilin-1-ameliorates-high-fat-diet-induced-insulin-resistance-via-suppression-of-nlrp3-inflammasome
#12
Xiaoyan Dai, Imoh Okon, Ming-Hui Zou
The history of neuropilin 1 (Nrp1) research is checkered with many unexpected and exciting findings. Nrp1 functions as a co-receptor for class 3 semaphorins, and several canonical growth factors, including vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). It has been implicated in the development of central nervous system, angiogenesis, and migration. Accumulating evidence demonstrates that Nrp1 is also highly expressed in immune cells, including macrophages and dendritic cells. Until now, the functions of Nrp1 within these cells remained poorly studied and elusive...
2017: Macrophage
https://www.readbyqxmd.com/read/29081352/development-of-the-hyaloid-choroidal-and-retinal-vasculatures-in-the-fetal-human-eye
#13
REVIEW
Gerard A Lutty, D Scott McLeod
The development of the ocular vasculatures is perfectly synchronized to provide the nutritional and oxygen requirements of the forming human eye. The fetal vasculature of vitreous, which includes the hyaloid vasculature, vasa hyaloidea propria, and tunica vasculosa lentis, initially develops around 4-6 weeks gestation (WG) by hemo-vasculogenesis (development of blood and blood vessels from a common progenitor, the hemangioblast). This transient fetal vasculature expands around 12 WG by angiogenesis (budding from primordial vessels) and remains until a retinal vasculature begins to form...
November 1, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/29071344/genetic-risk-variants-associated-with-comorbid-alcohol-dependence-and-major-depression
#14
Hang Zhou, Renato Polimanti, Bao-Zhu Yang, Qian Wang, Shizhong Han, Richard Sherva, Yaira Z Nuñez, Hongyu Zhao, Lindsay A Farrer, Henry R Kranzler, Joel Gelernter
Importance: Alcohol dependence (AD) and major depression (MD) are leading causes of disability that often co-occur. Genetic epidemiologic data have shown that AD and MD share a common possible genetic cause. The molecular nature of this shared genetic basis is poorly understood. Objectives: To detect genetic risk variants for comorbid AD and MD and to determine whether polygenic risk alleles are shared with neuropsychiatric traits or subcortical brain volumes. Design, Setting, and Participants: This genome-wide association study analyzed criterion counts of comorbid AD and MD in African American and European American data sets collected as part of the Yale-Penn study of the genetics of drug and alcohol dependence from February 14, 1999, to January 13, 2015...
October 25, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/29067024/multifaceted-role-of-neuropilins-in-the-immune-system-potential-targets-for-immunotherapy
#15
REVIEW
Sohini Roy, Arup K Bag, Rakesh K Singh, James E Talmadge, Surinder K Batra, Kaustubh Datta
Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29059194/role-of-neuropilin-1-semaphorin-3a-signaling-in-the-functional-and-morphological-integrity-of-the-cochlea
#16
Pezhman Salehi, Marshall X Ge, Usha Gundimeda, Leah Michelle Baum, Homero Lael Cantu, Joel Lavinsky, Litao Tao, Anthony Myint, Charlene Cruz, Juemei Wang, Angeliki Maria Nikolakopoulou, Carolina Abdala, Matthew William Kelley, Takahiro Ohyama, Thomas Matthew Coate, Rick A Friedman
Neuropilin-1 (Nrp1) encodes the transmembrane cellular receptor neuropilin-1, which is associated with cardiovascular and neuronal development and was within the peak SNP interval on chromosome 8 in our prior GWAS study on age-related hearing loss (ARHL) in mice. In this study, we generated and characterized an inner ear-specific Nrp1 conditional knockout (CKO) mouse line because Nrp1 constitutive knockouts are embryonic lethal. In situ hybridization demonstrated weak Nrp1 mRNA expression late in embryonic cochlear development, but increased expression in early postnatal stages when cochlear hair cell innervation patterns have been shown to mature...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29054606/semaphorin-4d-from-cd15-granulocytes-via-adam10-induced-cleavage-contributes-to-antibody-production-in-bullous-pemphigoid
#17
Shengxian Shen, Yao Ke, Erle Dang, Hui Fang, Yuqian Chang, Jieyu Zhang, Zhenlai Zhu, Shuai Shao, Pei Qiao, Tongmei Zhang, Hongjiang Qiao, Gang Wang
Autoreactive B cells activation and antibody production are critical events for the development of bullous pemphigoid (BP). However, the mechanism that is involved in the modulation of B cell activation and autoantibody generation has not been fully understood. Semaphorin 4D (Sema4D/CD100) plays important roles in immune regulation related to B cell, but its implication in BP remains obscure. The aim of our study was to characterize Sema4D and the underlying mechanism contributing to the autoimmune features of BP...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29048670/suppression-of-tumor-derived-semaphorin%C3%A2-7a-and-genetic-ablation-of-host-derived-semaphorin%C3%A2-7a-impairs-tumor-progression-in-a-murine-model-of-advanced-breast-carcinoma
#18
R Garcia-Areas, S Libreros, M Simoes, C Castro-Silva, N Gazaniga, S Amat, J Jaczewska, P Keating, K Schilling, M Brito, E P Wojcikiewicz, V Iragavarpu-Charyulu
Solid tumors can generate a plethora of neurogenesis-related molecules that enhance their growth and metastasis. Among them, we have identified axonal guidance molecule Semaphorin 7A (SEMA7A) in breast cancer. The goal of this study was to determine the therapeutic effect of suppressing SEMA7A levels in the 4T1 murine model of advanced breast carcinoma. We used anti-SEMA7A short hairpin RNA (shRNA) to gene silence SEMA7A in 4T1 mammary tumor cells. When implanted into the mammary fat pads of syngeneic mice, SEMA7A shRNA-expressing 4T1 tumors exhibited decreased growth rates, deferred metastasis and reduced mortality...
October 3, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29040270/analysis-of-the-interaction-of-plexin-b1-and-plexin-b2-with-rnd-family-proteins
#19
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/29029510/adenovirus-mediated-delivery-of-sema3a-alleviates-rheumatoid-arthritis-in-a-serum-transfer-induced-mouse-model
#20
Yue Teng, Zhanhai Yin, Jing Li, Kun Li, Xu Li, Yan Zhang
Rheumatoid arthritis is a chronic autoimmune disease characterized by infiltration of inflammatory cells into the synovium and destruction of cartilage and bone. Macrophages, fibroblast-like synoviocytes (FLS), and osteoclasts are critical cells driving the pathogenesis of RA. Semaphorin 3A (Sema3A) is recently identified as an essential player in the bone homeostasis, however its role in RA progression especially in the macrophage polarization are poorly understood. In the present study, we found that Sems3A levels were significantly decreased in RA serum and synovial fluid compared to OA controls...
September 12, 2017: Oncotarget
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