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https://www.readbyqxmd.com/read/28536997/plxna3-variant-rs5945430-is-associated-with-severe-clinical-course-in-male-multiple-sclerosis-patients
#1
Moaz Qureshi, Mohamed Hatem, Raed Alroughani, Sindhu P Jacob, Rabeah Abbas Al-Temaimi
Multiple sclerosis (MS) exhibits sex bias in disease clinical course as male MS patients develop severe, progressive clinical course with accumulating disability. So far, no factors have been found associating with this sex bias in MS severity. We set out to determine the genetic factor contributing to MS male-specific progressive disease. This is an MS cross-sectional study involving 213 Kuwaiti MS patients recruited at Dasman Diabetes Institute. Exome sequencing was performed on 18 females and 8 male MS patients' genomic DNA...
May 23, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28512129/mammalian-o-mannosylation-of-cadherins-and-plexins-is-independent-of-protein-o-mannosyltransferase-1-and-2
#2
Ida Signe Bohse Larsen, Yoshiki Narimatsu, Hiren Jitendra Joshi, Zhang Yang, Oliver J Harrison, Julia Brasch, Lawrence Shapiro, Barry Honig, Sergey Y Vakhrushev, Henrik Clausen, Adnan Halim
Protein O-mannosylation is found in yeast and metazoans and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies (CMD) designated α-dystroglycanopathies, because deficient O-Man glycosylation of -dystroglycan disrupts laminin interaction with -dystroglycan and the extracellular matrix...
May 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28508207/new-aspects-of-the-seam4d-dependent-control-of-lymphocyte-activation
#3
E M Kuklina, I V Nekrasova
Novel targets for action of the class IV semaphorin Seam4D have been identified in the immune system. The low-affinity CD72 receptor for Seam4D was detected not only on B lymphocytes, but also in a proportion of T cells, whereas the high-affinity semaphorin receptor, plexin B1, originally considered to belong to non-immune cells, proved to be in a great proportion of intact T and B cells. Seam4D is constitutively expressed in B cells, which, along with T cells, can serve as a source of both membrane and soluble semaphorin...
March 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28467912/plexin-b2-and-semaphorin-4c-guide-t-cell-recruitment-and-function-in-the-germinal-center
#4
Hu Yan, Longyan Wu, Changming Shih, Shiyue Hou, Jingwen Shi, Tianyang Mao, Wenbin Chen, Bhavani Melvin, Robert J Rigby, Yingjia Chen, Haochen Jiang, Roland H Friedel, Carola G Vinuesa, Hai Qi
Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28440030/-identification-of-target-genes-downstream-of-semaphorin6a-plexina2-signaling-in-zebrafish
#5
Sarah E Emerson, Riley M St Clair, Ashley L Waldron, Sierra R Bruno, Anna Duong, Heather E Driscoll, Bryan A Ballif, Sarah McFarlane, Alicia M Ebert
BACKGROUND: Semaphorin (Sema)/Plexin (Plxn) signaling is important for many aspects of neuronal development, however the transcriptional regulation imposed by this signaling pathway is unknown. Previously, we identified an essential role for Sema6A/PlxnA2 signaling in regulating proliferation and cohesion of retinal precursor cells (RPCs) during early eye development. This study used RNA isolated from control, Sema6A-deficient, and PlxnA2-deficient zebrafish embryos in a microarray analysis to identify genes that were differentially expressed when this signaling pathway was disrupted...
April 25, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28438183/semaphorin-plexin-signaling-influences-early-ventral-telencephalic-development-and-thalamocortical-axon-guidance
#6
Manuela D Mitsogiannis, Graham E Little, Kevin J Mitchell
BACKGROUND: Sensory processing relies on projections from the thalamus to the neocortex being established during development. Information from different sensory modalities reaching the thalamus is segregated into specialized nuclei, whose neurons then send inputs to cognate cortical areas through topographically defined axonal connections. Developing thalamocortical axons (TCAs) normally approach the cortex by extending through the subpallium; here, axonal navigation is aided by distributed guidance cues and discrete cell populations, such as the corridor neurons and the internal capsule (IC) guidepost cells...
April 24, 2017: Neural Development
https://www.readbyqxmd.com/read/28416516/semaphorin-4d-inhibits-neutrophil-activation-and-is-involved-in-the-pathogenesis-of-neutrophil-mediated-autoimmune-vasculitis
#7
Masayuki Nishide, Satoshi Nojima, Daisuke Ito, Hyota Takamatsu, Shohei Koyama, Sujin Kang, Tetsuya Kimura, Keiko Morimoto, Takashi Hosokawa, Yoshitomo Hayama, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Yoshimitsu Nakanishi, Takeshi Tsuda, Jeong Hoon Park, Toru Hirano, Yoshihito Shima, Masashi Narazaki, Eiichi Morii, Atsushi Kumanogoh
OBJECTIVES: Inappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to investigate the functions of semaphorin 4D (SEMA4D) in regulation of neutrophil activation, and its involvement in AAV pathogenesis. METHODS: Serum levels of soluble SEMA4D were evaluated by ELISA. Blood cell-surface expression of membrane SEMA4D was evaluated by flow cytometry. To determine the functional interactions between neutrophil membrane SEMA4D and endothelial plexin B2, wild-type and SEMA4D(-/-) mice neutrophils were cultured with an endothelial cell line (MS1) stained with SYTOX green, and subjected to neutrophil extracellular trap (NET) formation assays...
April 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28407732/transcriptome-profiling-reveals-expression-signatures-of-cranial-neural-crest-cells-arising-from-different-axial-levels
#8
Rachael Lumb, Sam Buckberry, Genevieve Secker, David Lawrence, Quenten Schwarz
BACKGROUND: Cranial neural crest cells (NCCs) are a unique embryonic cell type which give rise to a diverse array of derivatives extending from neurons and glia through to bone and cartilage. Depending on their point of origin along the antero-posterior axis cranial NCCs are rapidly sorted into distinct migratory streams that give rise to axial specific structures. These migratory streams mirror the underlying segmentation of the brain with NCCs exiting the diencephalon and midbrain following distinct paths compared to those exiting the hindbrain rhombomeres (r)...
April 13, 2017: BMC Developmental Biology
https://www.readbyqxmd.com/read/28407694/molecular-mechanisms-of-activating-c-met-in-kshv-primary-effusion-lymphoma
#9
Bao Quoc Lam, Lu Dai, Li Li, Jing Qiao, Zhen Lin, Zhiqiang Qin
The oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL), which is mostly seen in immunosuppressed patients. PEL is a rapidly progressing malignancy with a median survival time of approximately 6 months even under the conventional chemotherapy. We recently report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated in PEL cells and represents a promising therapeutic target (Blood. 2015;126(26):2821-31). However, the underlying mechanisms of c-MET activation within PEL cells remain largely unknown...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28338957/regulation-of-tgf-%C3%AE-mediated-endothelial-mesenchymal-transition-by-microrna-27
#10
Hiroshi I Suzuki, Akihiro Katsura, Hajime Mihira, Masafumi Horie, Akira Saito, Kohei Miyazono
Multiple microRNAs (miRNAs) regulate epithelial-mesenchymal transition and endothelial-mesenchymal transition (EndMT). Here we report that microRNA-27b (miR-27b) positively regulates transforming growth factor-β (TGF-β)-induced EndMT of MS-1 mouse pancreatic microvascular endothelial cells. TGF-β induced miR-23b/24-1/27b expression, and inhibition of miR-27 suppressed TGF-β-mediated induction of mesenchymal genes. Genome-wide miRNA target analysis revealed that miR-27 targets Elk1, which acts as a competitive inhibitor of myocardin-related transcription factor-serum response factor signalling and as a myogenic repressor...
May 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28334861/defective-signaling-through-plexin-a1-compromises-the-development-of-the-peripheral-olfactory-system-and-neuroendocrine-reproductive-axis-in-mice
#11
Séverine Marcos, Carine Monnier, Xavier Rovira, Corinne Fouveaut, Nelly Pitteloud, Fabrice Ango, Catherine Dodé, Jean-Pierre Hardelin
The olfacto-genital syndrome (Kallmann syndrome) associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency and anosmia. This is a genetically heterogeneous developmental disease with various modes of transmission, including oligogenic inheritance. Previous reports have involved defective cell signaling by semaphorin-3A in the disease pathogenesis. Here, we report that the embryonic phenotype of Plxna1-/- mutant mice lacking plexin-A1 (a major receptor of class 3 semaphorins), though not fully penetrant, resembles that of Kallmann syndrome fetuses...
June 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28281763/-15-n-h-related-conformational-entropy-changes-entailed-by-plexin-b1-rbd-dimerization-combined-molecular-dynamics-nmr-relaxation-approach
#12
Mirco Zerbetto, Eva Meirovitch
We report on a new method for determining function-related conformational entropy changes in proteins. Plexin-B1 RBD dimerization serves as example, and internally mobile N-H bonds serve as probes. Sk (entropy in units of kBT) is given by -∫(PeqlnPeq)dΩ, where Peq = exp(-u) is the probability density for probe orientation, and u the local potential. Previous slowly relaxing local structure (SRLS) analyses of (15)N-H relaxation in proteins determined linear combinations of D00(2)(Ω) and (D02(2)(Ω) + D0-2(2)(Ω)) (D0K(L)(Ω) represents a Wigner rotation matrix element in uniaxial local medium) as "best-fit" form of u...
March 30, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28280798/endometrial-expression-of-%C3%AE-3-integrin-calcitonin-and-plexin-b1-in-the-window-of-implantation-in-women-with-unexplained-infertility
#13
Mehran Dorostghoal, Hamid-O-Allah Ghaffari, Nahid Shahbazian, Maryam Mirani
BACKGROUND: Endometrial receptivity plays a key role in the establishment of successful implantation and its impairment may contribute to subfertility and limit the assisted reproduction techniques (ART) success. OBJECTIVE: The aim of present study was to investigate endometrial receptivity in terms of β3 integrin, calcitonin and plexin-B1 expression in women with unexplained infertility. MATERIALS AND METHODS: We evaluated expression of β3 integrin, calcitonin and plexin-B1 through mRNA level measurement with real-time RT-PCR, in the endometrium of 16 infertile women with unexplained infertility and 10 fertile women...
January 2017: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/28224988/post-endocytic-sorting-of-plexin-d1-controls-signal-transduction-and-development-of-axonal-and-vascular-circuits
#14
Katja Burk, Erik Mire, Anaïs Bellon, Mélanie Hocine, Jeremy Guillot, Filipa Moraes, Yutaka Yoshida, Michael Simons, Sophie Chauvet, Fanny Mann
Local endocytic events involving receptors for axon guidance cues play a central role in controlling growth cone behaviour. Yet, little is known about the fate of internalized receptors, and whether the sorting events directing them to distinct endosomal pathways control guidance decisions. Here, we show that the receptor Plexin-D1 contains a sorting motif that interacts with the adaptor protein GIPC1 to facilitate transport to recycling endosomes. This sorting process promotes colocalization of Plexin-D1 with vesicular pools of active R-ras, leading to its inactivation...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28215559/soxc-transcription-factors-promote-contralateral-retinal-ganglion-cell-differentiation-and-axon-guidance-in-the-mouse-visual-system
#15
Takaaki Kuwajima, Célia A Soares, Austen A Sitko, Véronique Lefebvre, Carol Mason
Transcription factors control cell identity by regulating diverse developmental steps such as differentiation and axon guidance. The mammalian binocular visual circuit is comprised of projections of retinal ganglion cells (RGCs) to ipsilateral and contralateral targets in the brain. A transcriptional code for ipsilateral RGC identity has been identified, but less is known about the transcriptional regulation of contralateral RGC development. Here we demonstrate that SoxC genes (Sox4, 11, and 12) act on the progenitor-to-postmitotic transition to implement contralateral, but not ipsilateral, RGC differentiation, by binding to Hes5 and thus repressing Notch signaling...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28122739/the-integrin-psi-domain-has-an-endogenous-thiol-isomerase-function-and-is-a-novel-target-for-antiplatelet-therapy
#16
Guangheng Zhu, Qing Zhang, Emily C Reddy, Naadiya Carrim, Yunfeng Chen, Xiaohong Ruby Xu, Miao Xu, Yiming Wang, Yan Hou, Li Ma, Yan Li, Min Rui, Tania N Petruzziello-Pellegrini, Christopher Lavalle, Tyler W Stratton, Xi Lei, Reheman Adili, Pingguo Chen, Cheng Zhu, John A Wilkins, Richard O Hynes, John Freedman, Heyu Ni
Integrins are a large family of heterodimeric transmembrane receptors differentially expressed on almost all metazoan cells. Integrin β subunits contain a highly conserved plexin-semaphorin-integrin (PSI) domain. The CXXC motif, the active site of the protein-disulfide-isomerase (PDI) family, is expressed twice in this domain of all integrins across species. However, the role of the PSI domain in integrins and whether it contains thiol-isomerase activity have not been explored. Here, recombinant PSI domains of murine β3, and human β1 and β2 integrins were generated and their PDI-like activity was demonstrated by refolding of reduced/denatured RNase...
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28103666/molecular-dynamics-simulations-reveal-isoform-specific-contact-dynamics-between-the-plexin-rho-gtpase-binding-domain-rbd-and-small-rho-gtpases-rac1-and-rnd1
#17
Liqun Zhang, Matthias Buck
The Plexin family of transmembrane receptors are unique in that their intracellular region interacts directly with small GTPases of the Rho family. The Rho GTPase binding domain of plexin (RBD)-which is responsible for these interactions-can bind with Rac1 as well as Rnd1 GTPases. GTPase complexes have been crystallized with the RBDs of plexinA1, -A2, and -B1. The protein association is thought to elicit different functional responses in a GTPase and plexin isoform specific manner, but the origin of this is unknown...
February 8, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28052247/sema-1a-reverse-signaling-promotes-midline-crossing-in-response-to-secreted-semaphorins
#18
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
#19
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...
February 2017: 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
#20
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
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