Trka Mediates Retrograde Semaphorin 3A Signaling Through Plexin A4 To
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Neural Map Formation in the Mouse Olfactory System
Cell. Mol. Life Sci. (2014) 71:3049–3057 DOI 10.1007/s00018-014-1597-0 Cellular and Molecular Life Sciences REVIEW Neural map formation in the mouse olfactory system Haruki Takeuchi · Hitoshi Sakano Received: 25 November 2013 / Revised: 26 February 2014 / Accepted: 27 February 2014 / Published online: 18 March 2014 © The Author(s) 2014. This article is published with open access at Springerlink.com Abstract In the mouse olfactory system, odorants are Introduction detected by ~1,000 different odorant receptors (ORs) pro- duced by olfactory sensory neurons (OSNs). Each OSN In the mouse, various odorants are detected with approxi- expresses only one functional OR species, which is referred mately 1,000 different odorant receptors (ORs) expressed to as the “one neuron–one receptor” rule. Furthermore, OSN in the olfactory sensory neurons (OSNs) [1]. Each OSN in axons bearing the same OR converge to a specific projection the olfactory epithelium (OE) expresses only one functional site in the olfactory bulb (OB) forming a glomerular struc- OR gene in a mono-allelic manner [2]. Furthermore, OSNs ture, i.e., the “one glomerulus–one receptor” rule. Based on expressing the same OR converge their axons to a spe- these basic rules, binding signals of odorants detected by cific pair of glomeruli at stereotyped locations in the olfac- OSNs are converted to topographic information of activated tory bulb (OB) (Fig. 1a, b) [3]. Thus, the odor information glomeruli in the OB. During development, the glomerular detected in the OE is topographically represented as the pat- map is formed by the combination of two genetically pro- tern of activated glomeruli in the OB (Fig. -
The Role of Semaphorins and Their Receptors in Vascular Development and Cancer
EXPERIMENTAL CELL RESEARCH ] ( ]]]]) ]]]– ]]] Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/yexcr Review Article The role of semaphorins and their receptors in vascular development and cancer Chenghua Gua,n, Enrico Giraudob,nn aDepartment of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA 02115, USA bInstitute for Cancer Research at Candiolo (IRC@C), and Department of Science and Drug Technology, University of Torino, Str. Prov. 142 Km.3,95 10060 Candiolo, Turin, Italy article information abstract Article Chronology: Semaphorins (Semas) are a large family of traditional axon guidance molecules. Through Received 1 February 2013 interactions with their receptors, Plexins and Neuropilins, Semas play critical roles in a Accepted 6 February 2013 continuously growing list of diverse biological systems. In this review, we focus on their function in regulating vascular development. In addition, over the past few years a number of Keywords: findings have shown the crucial role that Semas and their receptors play in the regulation of Semaphorin cancer progression and tumor angiogenesis. In particular, Semas control tumor progression by Plexin directly influencing the behavior of cancer cells or, indirectly, by modulating angiogenesis and Neuropilin the function of other cell types in the tumor microenvironment (i.e., inflammatory cells and Angiogenesis fibroblasts). Some Semas can activate or inhibit tumor progression and angiogenesis, while Cancer others may have the opposite effect depending on specific post-translational modifications. Here Tumor we will also discuss the diverse biological effects of Semas and their receptor complexes on Development cancer progression as well as their impact on the tumor microenvironment. & Vasculature 2013 Elsevier Inc. -
Plexin A4 (PLXNA4) (NM 181775) Human Recombinant Protein – TP761981 | Origene
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP761981 Plexin A4 (PLXNA4) (NM_181775) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Purified recombinant protein of Human plexin A4 (PLXNA4), transcript variant 2,full length, with N-terminal GST and C-terminal His tag, expressed in E. coli, 50ug Species: Human Expression Host: E. coli Tag: N-GST and C-His Predicted MW: 86 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25mM Tris, pH8.0, 150 mM NaCl, 10% glycerol,1% Sarkosyl. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_861440 Locus ID: 91584 UniProt ID: Q9HCM2 RefSeq Size: 2020 Cytogenetics: 7q32.3 RefSeq ORF: 1566 Synonyms: FAYV2820; PLEXA4; PLXNA4A; PLXNA4B; PRO34003 Summary: Coreceptor for SEMA3A. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm (By similarity).[UniProtKB/Swiss-Prot Function] Protein Families: Druggable Genome This product is to be used for laboratory only. -
The Involvement of Rho Gtpases in Plexin Mediated Signal Transduction
The Involvement of Rho GTPases in Plexin Mediated Signal Transduction Laura Turner A thesis submitted to the University of London for the degree of Doctor of Philosophy November 2003 MRC Laboratory for Molecular Cell Biology University of London Gower Street London WCIE 6BT ProQuest Number: U642461 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U642461 Published by ProQuest LLC(2015). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT Plexins are a family of conserved transmembrane proteins. Together with neuropilins, they act as receptors for the semaphorin family of growth cone guidance molecules. Whilst it is clear that guidance involves cytoskeletal changes, little is known of the mechanisms via which plexins regulate growth cone morphology. Hints suggesting the involvement of Rho GTPases stem from observations of localised actin rearrangements elicited by plexins and semaphorins. This feeling is consolidated by the demonstration of the Rac dependent nature of plexin induced cellular responses. To investigate plexin mediated signal transduction, a heterologous assay for semaphorin induced collapse has been developed and characterised. Studies using jasplakinolide indicate that Sema3A-Fc induced collapse requires actin dissassembly. -
Expression of a Mirna Targeting Mutated SOD1 in Astrocytes Induces Motoneuron Plasticity and Improves Neuromuscular Function in ALS Mice
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.08.425706; this version posted January 9, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Expression of a miRNA targeting mutated SOD1 in astrocytes induces motoneuron plasticity and improves neuromuscular function in ALS mice Rochat C.1, Bernard-Marissal N.1,6, Pradervand S.3, Perrin F.E.4, Raoul C.5, Aebischer P.1, Schneider B.L.1,2* 1 Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland 2 Bertarelli Platform for Gene Therapy, Ecole Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland 3 Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland. 4 INSERM U1198, University of Montpellier, EPHE, Place Eugène Bataillon CC105, F-34095, Montpellier, France 5 The Neuroscience Institute of Montpellier, Inserm UMR1051, Univ Montpellier, Saint Eloi Hospital, Montpellier, France 6 Aix Marseille Univ, INSERM, MMG, Marseille, France *Correspondence should be addressed to B.L.S. ([email protected]) Short title: miRNA gene therapy targeting astrocytes in ALS Study was performed in Lausanne, Switzerland Current address of corresponding author: Bernard Schneider EPFL SV PTECH PTBTG Ch. des Mines 9 CH-1202 Genève Switzerland Email: [email protected] Tel: +41 21 693 95 05 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.08.425706; this version posted January 9, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
The Expression of Key Guidance Genes at a Forebrain Axon Turning Point Is Maintained by Distinct Fgfr Isoforms but a Common Downstream Signal Transduction Mechanism
New Research Development The Expression of Key Guidance Genes at a Forebrain Axon Turning Point Is Maintained by Distinct Fgfr Isoforms but a Common Downstream Signal Transduction Mechanism Jung-Lynn Jonathan Yang, Gabriel E. Bertolesi, Stephanie Dueck, Carrie L. Hehr, and Sarah McFarlane https://doi.org/10.1523/ENEURO.0086-19.2019 Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada Abstract During development the axons of neurons grow toward and locate their synaptic partners to form functional neural circuits. Axons do so by reading a map of guidance cues expressed by surrounding tissues. Guidance cues are expressed at a precise space and time, but how guidance cue expression is regulated, and in a coordinated manner, is poorly understood. Semaphorins (Semas) and Slits are families of molecular ligands that guide axons. We showed previously that fibroblast growth factor (Fgf) signaling maintains sema3a and slit1 forebrain expres- sion in Xenopus laevis, and these two repellents cooperate to guide retinal ganglion cell (RGC) axons away from the mid-diencephalon and on towards the optic tectum. Here, we investigate whether there are common features of the regulatory pathways that control the expression of these two guidance cues at this single axon guidance decision point. We isolated the sema3a proximal promoter and confirmed its responsiveness to Fgf signaling. Through misexpression of truncated Fgf receptors (Fgfrs), we found that sema3a forebrain expression is dependent on Fgfr2-4 but not Fgfr1. This is in contrast to slit1, whose expression we showed previously depends on Fgfr1 but not Fgfr2-4. -
Spatial and Temporal Second Messenger Codes for Growth Cone Turning
Spatial and temporal second messenger codes for growth cone turning Xavier Nicol1,2, Kwan Pyo Hong, and Nicholas C. Spitzer Neurobiology Section, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California at San Diego, La Jolla, CA 92093 Edited* by Lynn T. Landmesser, Case Western Reserve University, Cleveland, OH, and approved July 5, 2011 (received for review January 6, 2011) Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent se- generated in growth cones in response to Netrin-1, the principal cond messengers that regulate a wide range of cellular processes. axon guidance molecule required for attraction of commissural During development of neuronal networks they are critical for the axons by the spinal floor plate. We report a major difference in first step of circuit formation, transducing signals required for axon cAMP/calcium interplay between filopodia and the growth cone fi pathfinding. Surprisingly, the spatial and temporal cAMP and cal- center. Optogenetic elevation of cAMP in lopodia but not in fi cium codes used by axon guidance molecules are unknown. Here, growth cone centers drives growth cone attraction. Both lopo- we identify characteristics of cAMP and calcium transients gener- dial and growth cone center signaling pathways are mediated by ated in growth cones during Netrin-1–dependent axon guidance. In activation of the same Netrin-1 receptor, Deleted in Colorectal Cancer (DCC). We show that cAMP dynamics are also essential filopodia, Netrin-1–dependent Deleted in Colorectal Cancer (DCC) for midline crossing of commissural axons in vivo. receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. -
Regulation of Axonal Development by Natriuretic Peptide Hormones
Regulation of axonal development by natriuretic peptide hormones Zhen Zhao and Le Ma1 Zilkha Neurogenetic Institute, Department of Cell and Neurobiology, Keck School of Medicine, Neuroscience Graduate Program, University of Southern California, 1501 San Pablo Street, Los Angeles, CA 90089 Edited by Cornelia I. Bargmann, The Rockefeller University, New York, NY, and approved August 28, 2009 (received for review June 24, 2009) Natriuretic peptides (NPs) are a family of cardiac- and vascular- entially binds to Npr2, could be the environmental cue respon- derived hormones that are well known for regulating blood sible for generating bifurcated axonal branches. These results pressure, but their expression in the brain poses an intriguing yet suggest an intriguing hypothesis that NPs provide a general unanswered question concerning their roles in the nervous system. extracellular mechanism to regulate different processes, such as Here, we report several unique activities of these hormones in branching and guidance, during axonal development via the regulating axonal development of dorsal root ganglion (DRG) regulation of cGMP signaling. neurons in the spinal cord. First, the C-type NP (CNP) is expressed To test this hypothesis, we first examined a spontaneous in a restricted area of the dorsal spinal cord and provides a cue that mouse mutant with a mutation in the Nppc gene encoding the is necessary for bifurcation of central sensory afferents. Second, in CNP precursor and found a similar bifurcation defect during the culture of embryonic DRG neurons, CNP stimulates branch sensory afferent development. In addition, we conducted a formation, induces axon outgrowth, and attracts growth cones. systematic analysis of the functions of NPs in axonal develop- Furthermore, these activities are mediated by cyclic guanosine- ment by using the primary culture of DRG neurons. -
Sema4a Induces Cell Morphological Changes Through B-Type Plexin-Mediated Signaling
225-230.qxd 18/12/2009 10:31 Ì Page 225 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 25: 225-230, 2010 225 Sema4A induces cell morphological changes through B-type plexin-mediated signaling KAZUNORI YUKAWA1, TETSUJI TANAKA2, KENJI YOSHIDA1, NORIKO TAKEUCHI1, TAKUJI ITO1, HYOTA TAKAMATSU3, HITOSHI KIKUTANI4 and ATSUSHI KUMANOGOH3 1Department of Physiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503; 2Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509; Department of 3Immunopathology; 4Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Received September 14, 2009; Accepted November 6, 2009 DOI: 10.3892/ijmm_00000334 Abstract. Semaphorins are a family of secreted and membrane- compared with the control plasmid. Sema4A thus induces bound proteins known as axonal pathfinders. Sema4A, a growth cone collapse through the down-regulation of R-Ras member of class 4 semaphorins, induces growth cone collapse activity in mouse hippocampal neurons. of hippocampal neurons. The binding of Sema4A to growth cones indicates the presence of receptors transmitting signals Introduction through the intracellular effectors to induce growth cone collapse in hippocampal neurons. Transfection experiments Semaphorins compose a large family of phylogenetically of the candidate receptor genes into COS-7 cells conserved soluble and transmembrane molecules, which are demonstrated that Sema4A binds to axonal guidance further divided into eight classes (1). Semaphorins were receptors Plexin-B1, -B2 and -B3. To identify the functional originally identified as repulsive axonal guidance cues which Sema4A receptor and the signal transduction machinery, induce growth cone collapse in developing neurons (2-4). -
Regulatory T Cells Modulate Granulomatous Inflammation in an HLA-DP2 Transgenic Murine Model of Beryllium-Induced Disease
Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease Douglas G. Macka, Michael T. Faltaa, Amy S. McKeea, Allison K. Martina, Philip L. Simoniana, Frances Crawfordb,c, Terry Gordond, Robert R. Mercere, Mark D. Hoovere, Philippa Marrackb,c, John W. Kapplerb,c,1, Rubin M. Tudera, and Andrew P. Fontenota,b,1 Departments of aMedicine and bImmunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; dDepartment of Environmental Medicine, New York University, Tuxedo, NY 10987; eNational Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505; and cHoward Hughes Medical Institute, National Jewish Health, Denver, CO 80206 Contributed by John W. Kappler, May 2, 2014 (sent for review March 10, 2014) Susceptibility to chronic beryllium disease (CBD) is linked to certain a determination of the factors that contribute to their presence in HLA-DP molecules, including HLA-DP2. To elucidate the molecular the lung. basis of this association, we exposed mice transgenic (Tg) for HLA- Here, we exposed mice transgenic (Tg) for HLA-DP2 (the most DP2 to beryllium oxide (BeO) via oropharyngeal aspiration. As prevalent βGlu69-containing molecule) to Be oxide (BeO), a form opposed to WT mice, BeO-exposed HLA-DP2 Tg mice developed of the metal that is used in the workplace. BeO-exposed HLA- mononuclear infiltrates in a peribronchovascular distribution that DP2–expressing mice developed mononuclear infiltrates in the + were composed of CD4 T cells and included regulatory T (Treg) cells. lung, a Be-specific adaptive immune response in lung and spleen, Beryllium-responsive, HLA-DP2–restricted CD4+ T cells expressing andanexpansionofTreg cells in the lung. -
Products for Semaphorin Research
RnDSy-lu-2945 Products for Semaphorin Research Axon Guidance & Photoreceptor Development Cancer & Metastasis Immune Function Angiogenesis Bone Formation Semaphorins, Plexins, Neuropilins, and Related Molecules Initially characterized as axon guidance cues, Semaphorins have since been shown to mediate a wide range of biological activities including lymphocyte activation, photoreceptor development and survival, angiogenesis, bone remodeling, cell migration, oncogenesis, and phototransduction. Given the broad scope of biological activities, it is not surprising that defects in Semaphorin activity have been implicated in a number of pathological conditions including retinal degeneration, oncogenesis, and neurodegenerative disorders. Semaphorins are an evolutionarily conserved family of secreted and membrane-associated proteins that have been divided into eight subclasses based on sequence and structural similarity. Class 1 and 2 Semaphorins are expressed in invertebrates, Class are expressed in vertebrates, and the eighth class, referred to as Class V, includes Semaphorins that are expressed in viruses. Although most Semaphorins share less than 50% amino acid identity, all contain a conserved extracellular domain of approximately 500 amino acids known as the Semaphorin (sema) domain. The sema domain contains several highly conserved cysteine residues and a beta propeller structural motif that is found in other multi-functional proteins such as Integrins. The diverse biological activities mediated by Semaphorins can be attributed to differences in their expression patterns, receptor binding and mechanisms of signal transduction. Secreted Semaphorins (Classes 2, 3, and V) serve as ligands to elicit biological responses, while membrane- associated Semaphorins (Classes 1, 4, 6, and 7) not only serve as ligands, but also as receptors capable of mediating reverse signaling. Several receptors, co-receptors, and receptor binding partners have been identified, but Plexins and Neuropilins act as the primary Semaphorin recep- tors. -
Plexin-B1 Mutations in Prostate Cancer
Plexin-B1 mutations in prostate cancer Oscar Gee-Wan Wong*, Tharani Nitkunan*, Izumi Oinuma†, Chun Zhou*, Veronique Blanc*, Richard S. D. Brown*, Simon R. J. Bott*, Joseph Nariculam*, Gary Box‡, Phillipa Munson§, Jason Constantinou*, Mark R. Feneley*, Helmut Klocker¶, Suzanne A. Eccles‡, Manabu Negishi†, Alex Freeman§, John R. Masters*, and Magali Williamson*ʈ *Prostate Cancer Research Centre, Institute of Urology, University College London, 67 Riding House Street, London W1W 7EJ, United Kingdom; †Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan; ‡Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom; §Department of Histopathology, University College London, London WC1E 6BT, United Kingdom; and ¶Department of Urology, University of Innsbruck, 6020 Innsbruck, Austria Edited by Stanley M. Gartler, University of Washington, Seattle, WA, and approved September 28, 2007 (received for review March 19, 2007) Semaphorins are a large class of secreted or membrane-associated The cytoplasmic domain and part of the extracellular domain proteins that act as chemotactic cues for cell movement via their (exons 1–5) of plexins A1, A3, and B1 were sequenced using cDNA transmembrane receptors, plexins. We hypothesized that the func- from the human prostate cancer cell lines PC3, DU145, and tion of the semaphorin signaling pathway in the control of cell LNCaP. A single nucleotide change (A5359G) was found in migration could be harnessed by cancer cells during invasion and Plexin-B1 in LNCaP, which potentially changes threonine 1697 to metastasis. We now report 13 somatic missense mutations in the an alanine. The A5359G mutation alters a BstZ171 site, and cytoplasmic domain of the Plexin-B1 gene.