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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
Jeannine Muller-Greven, SoonJeung Kim, Prasanta K Hota, Yufeng Tong, Susmita Borthakur, Matthias Buck
Plexins are unique, as they are the first example of a transmembrane receptor that interacts directly with small GTPases, a family of proteins that are essential for cell motility and proliferation/survival. We and other laboratories have determined the structure of the Rho GTPase-binding domain (RBD) of several plexins and also of the entire intracellular region of plexin-B1. Structures of plexin complexes with Rho GTPases, Rac1 and Rnd1, and a structure with a Ras GTPase, Rap1b, have also been solved. The relationship between plexin-Rho and plexin-Ras interactions is still unclear and in vitro biophysical experiments that characterize the protein interactions of purified components play an important role in advancing our understanding of the molecular mechanisms that underlie the function of plexin...
2017: Methods in Molecular Biology
Keishi Otsu, Hiroko Ida-Yonemochi, Naoki Fujiwara, Hidemitsu Harada
During tooth development, oral epithelial cells differentiate into ameloblasts in order to form the most mineralized tissue in the vertebrate body: enamel. During this process, ameloblasts directionally secrete enamel matrix proteins and morphologically change from low columnar cells to polarized tall columnar cells, both of which are essential for the proper formation of enamel. In this study, we elucidated the molecular mechanism that integrates ameloblast function and morphology. Immunohistochemistry revealed that the restricted expression of semaphorin 4D (Sema4D) and RhoA activation status are closely associated with ameloblast differentiation in mouse incisors...
May 24, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Yingwei Chang, Li Li, Luping Zhang, Xuyan Guo, Zhuoying Feng, Junchen Zhou, Shuai Zhou, Guoying Feng, Fengchan Han, Wenhua Huang, Jun Yang, Fei Huang
Gliomas are one of the most common primary brain tumors in adults. They display aggressive invasiveness, are highly vascular, and have a poor prognosis. Plexin-B1 is involved in numerous cellular processes, especially cellular migration and angiogenesis. However, the role and regulatory mechanisms of Plexin-B1 in gliomas are not understood and were thus investigated in this study. By using multiple and diverse experimental techniques, we investigated cell apoptosis, mitochondrial membrane potential, cell migration and invasion, angiogenesis, PI3K and Akt phosphorylation, and also the levels of SRPK1 and αvβ3 in glioma cells and animal glioma tissues...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Oren Tchaicheeyan, Jack H Freed, Eva Meirovitch
Restricted motions in proteins (e.g., N-H bond dynamics) are studied effectively with NMR. By analogy with restricted motions in liquid crystals (LC), the local ordering has in the past been primarily represented by potentials comprising the L = 2, |K| = 0, 2 spherical harmonics. However, probes dissolved in LCs experience nonpolar ordering, often referred to as alignment, while protein-anchored probes experience polar ordering, often referred to as orientation. In this study we investigate the role of local (site) symmetry in the context of the polarity of the local ordering...
March 24, 2016: Journal of Physical Chemistry. B
Ying-Hua Yang, Asma Buhamrah, Abraham Schneider, Yi-Ling Lin, Hua Zhou, Amr Bugshan, John R Basile
Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption...
2016: PloS One
Mingfu Wu, Jing Li, Qinglei Gao, Fei Ye
INTRODUCTION: Semaphorin 4D (Sema4D), also known as CD100, has been implicated in physiologic roles in the immune and nervous systems. However, the interaction of Sema4D with its high affinity receptor, Plexin-B1, reveals a novel role for Sema4D produced by the tumor microenvironment in tumor angiogenesis and metastasis. AREAS COVERED: The ligation of Sema4D/CD100 with CD72 on immune and inflammatory cells is known to stimulate immune responses and regulation. Because CD100 and CD72 are expressed on lung immune and nonimmune cells, as well as on mast cells, the CD100/CD72 interaction plays another important role in allergic airway inflammation and mast cell functions...
July 2016: Expert Opinion on Therapeutic Targets
Fatemeh Sharifpanah, Sepali De Silva, Mohamed M Bekhite, Jorge Hurtado-Oliveros, Klaus T Preissner, Maria Wartenberg, Heinrich Sauer
OBJECTIVE: Cell injury releases nucleic acids supporting inflammation and stem cell activation. Here, the impact of extracellular ribonucleic acid, especially transfer RNA (ex-tRNA), on vasculogenesis and leukopoiesis of mouse embryonic stem (ES) cells was investigated. APPROACH AND RESULTS: ex-tRNA, whole cell RNA and ribosomal RNA (ex-rRNA) but not DNA increased CD31-positive vascular structures in embryoid bodies. Ex-tRNA and ex-rRNA increased numbers of VEGFR2(+), CD31(+) and VE-cadherin(+) vascular cells as well as CD18(+), CD45(+) and CD68(+) cells, indicating leukocyte/macrophage differentiation...
December 2015: Free Radical Biology & Medicine
Xiao-li Liu, Jing Song, Ke-jian Liu, Wen-peng Wang, Chang Xu, Yu-zeng Zhang, Yun Liu
Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway...
October 2015: Journal of Huazhong University of Science and Technology. Medical Sciences
Sebastián Quintremil, Carolina Alberti, Matías Rivera, Fernando Medina, Javier Puente, Luis Cartier, Eugenio Ramírez, Yuetsu Tanaka, M Antonieta Valenzuela
Human lymphotropic virus type 1 (HTLV-1) is a retrovirus causing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurodegenerative central nervous system (CNS) axonopathy. This virus mainly infects CD4(+) T lymphocytes without evidence of neuronal infection. Viral Tax, secreted from infected lymphocytes infiltrated in the CNS, is proposed to alter intracellular pathways related to axonal cytoskeleton dynamics, producing neurological damage. Previous reports showed a higher proteolytic release of soluble Semaphorin 4D (sSEMA-4D) from CD4(+) T cells infected with HTLV-1...
January 2016: AIDS Research and Human Retroviruses
Lin Wang, Guanhua Song, Yabing Zheng, Weiwei Tan, Jihong Pan, Yu Zhao, Xiaotian Chang
INTRODUCTION: Semaphorin 4A (Sema4A) plays critical roles in many physiological and pathological processes including neuronal development, angiogenesis, immune response regulation, autoimmunity, and infectious diseases. The present study aimed to investigate its expression and biological activity in rheumatoid arthritis (RA). METHODS: RNA and protein were isolated from synovial tissues in RA and osteoarthritis (OA) patients. Treatment with recombinant human Sema4A (rhSema4A) or small interfering RNA (siRNA) was applied to examine its effect on the biological activity of synovial fibroblasts of RA (RASFs)...
2015: Arthritis Research & Therapy
Maria Carolina A Luque, Paulo S Gutierrez, Victor Debbas, Jorge Kalil, Beatriz S Stolf
Leukocyte migration is essential for the function of the immune system. Their recruitment from the vessels to the tissues involves sequential molecular interactions between leukocytes and endothelial cells (ECs). Many adhesion molecules involved in this process have already been described. However, additional molecules may be important in this interaction, and here we explore the potential role for CD100 and plexins in monocyte-EC binding. CD100 was shown to be involved in platelet-endothelial cell interaction, an important step in atherogenesis and thrombus formation...
October 2015: Molecular Immunology
Jiao Cao, Chen Zhang, Ting Chen, Rong Tian, Shuhong Sun, Xianshui Yu, Chunying Xiao, Gang Wang, Yufeng Liu, Meng Fu, Wei Li
BACKGROUND OBJECTIVES: Semaphorin 4D (Sema4D) and its receptor, Plexin-B1, are involved in the pathogenesis of squamous cell carcinoma (SCC) by mediating angiogenesis or perineural invasion through the interaction between Sema4D expression on SCC cells and Plexin-B1 expression on endothelial cells or nerves. Plexin-B1 was also recently found to be expressed on SCC cells. Plexin-B1 expression on several types of tumor cells could mediate various, and occasionally opposing, effects, including tumor cell survival, proliferation, angiogenesis, invasion, and metastasis...
August 2015: Journal of Dermatological Science
Muhammad Faraz Arshad Malik, Lin Ye, Wen G Jiang
Involvement of semaphorin 4D (Sema4D) and the receptor proteins of the plexins B family (plexin-B1, -B2 and -B3) in solid tumours suggests they play a role in breast cancer. In the present study, the expression of Sema4D and plexin-Bs was examined in a breast cancer cohort. The expression of Sema4D and plexin-Bs was examined in 147 tumours together with 22 normal mammary tissues using quantitative PCR along with clinicopathological patient data, as well as in MCF-7 and MDA-MB-231 cell lines treated with selective oestrogen receptor modulators (SERMs)...
August 2015: Oncology Reports
Piret Laht, Epp Tammaru, Maarja Otsus, Johan Rohtla, Liivi Tiismus, Andres Veske
Molecular mechanisms underlying synaptogenesis and synaptic plasticity have become one of the main topics in neurobiology. Increasing evidence suggests that axon guidance molecules including semaphorins and plexins participate in synapse formation and elimination. Although class B plexins are widely expressed in the brain, their role in the nervous system remains poorly characterized. We previously identified that B-plexins modulate microtubule dynamics and through this impact dendrite growth in rat hippocampal neurons...
July 15, 2015: Experimental Cell Research
M Williamson, P de Winter, J R Masters
Semaphorins and their receptors plexins have diverse roles in many cancers affecting tumour growth, metastasis and angiogenesis. Plexin-B1, the receptor for semaphorin4D (Sema4D), has been implicated in prostate cancer where mutation of the gene and overexpression of the protein occur. It is not clear, however, as to which of the several Sema4D-activated signalling pathways downstream of plexin-B1 function in prostate cancer progression. We show here that Sema4D/plexin-B1 increases the expression of androgen-responsive genes and activates the transcriptional activity of the androgen receptor (AR)...
February 25, 2016: Oncogene
Liqun Zhang, Anton Polyansky, Matthias Buck
Single-pass transmembrane (TM) receptors transmit signals across lipid bilayers by helix association or by configurational changes within preformed dimers. The structure determination for such TM regions is challenging and has mostly been accomplished by NMR spectroscopy. Recently, the computational prediction of TM dimer structures is becoming recognized for providing models, including alternate conformational states, which are important for receptor regulation. Here we pursued a strategy to predict helix oligomers that is based on packing considerations (using the PREDDIMER webserver) and is followed by a refinement of structures, utilizing microsecond all-atom molecular dynamics simulations...
2015: PloS One
Elizabeth E Evans, Alan S Jonason, Holm Bussler, Sebold Torno, Janaki Veeraraghavan, Christine Reilly, Michael A Doherty, Jennifer Seils, Laurie A Winter, Crystal Mallow, Renee Kirk, Alan Howell, Susan Giralico, Maria Scrivens, Katya Klimatcheva, Terrence L Fisher, William J Bowers, Mark Paris, Ernest S Smith, Maurice Zauderer
Semaphorin 4D (SEMA4D, CD100) and its receptor plexin-B1 (PLXNB1) are broadly expressed in murine and human tumors, and their expression has been shown to correlate with invasive disease in several human tumors. SEMA4D normally functions to regulate the motility and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. In the setting of cancer, SEMA4D-PLXNB1 interactions have been reported to affect vascular stabilization and transactivation of ERBB2, but effects on immune-cell trafficking in the tumor microenvironment (TME) have not been investigated...
June 2015: Cancer Immunology Research
Wenhao Wang, Tao Zhang, Genxi Zhang, Jinyu Wang, Kunpeng Han, Yongjuan Wang, Yinwen Zhang
Newcastle disease (ND) and avian infectious bronchitis (IB) are contagious diseases of chickens. To identify genes associated with antibody levels against ND and IB, a genome-wide association study was performed using specific-locus amplified fragment sequencing (SLAF-seq) technology in Jinghai yellow chickens. This determined six single-nucleotide polymorphisms (SNPs) that were associated with antibody levels against Newcastle disease virus (NDV): rsZ2494661, rsZ2494710, rs1211307701, rs1211307711, rs1218289310 and rs420701988...
August 2015: Journal of Applied Genetics
Tomoyo Okada, Surajit Sinha, Ilaria Esposito, Gaia Schiavon, Miguel A López-Lago, Wenjing Su, Christine A Pratilas, Cristina Abele, Jonathan M Hernandez, Masahiro Ohara, Morihito Okada, Agnes Viale, Adriana Heguy, Nicholas D Socci, Anna Sapino, Venkatraman E Seshan, Stephen Long, Giorgio Inghirami, Neal Rosen, Filippo G Giancotti
We identified the Rho GTPase Rnd1 as a candidate metastasis suppressor in basal-like and triple-negative breast cancer through bioinformatics analysis. Depletion of Rnd1 disrupted epithelial adhesion and polarity, induced epithelial-to-mesenchymal transition, and cooperated with deregulated expression of c-Myc or loss of p53 to cause neoplastic conversion. Mechanistic studies revealed that Rnd1 suppresses Ras signalling by activating the GAP domain of Plexin B1, which inhibits Rap1. Rap1 inhibition in turn led to derepression of p120 Ras-GAP, which was able to inhibit Ras...
January 2015: Nature Cell Biology
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