Structure and functional relevance of the Slit2 homodimerization domain
Identifieur interne : 002856 ( Main/Exploration ); précédent : 002855; suivant : 002857Structure and functional relevance of the Slit2 homodimerization domain
Auteurs : Elena Seiradake [France] ; Anne C. Von Philipsborn [Allemagne] ; Maud Henry [France] ; Martin Fritz [Allemagne] ; Hugues Lortat-Jacob [France] ; Marc Jamin [France] ; Wieger Hemrika [Pays-Bas] ; Martin Bastmeyer [Allemagne] ; Stephen Cusack [France] ; Andrew A. Mccarthy [France]Source :
- EMBO reports [ 1469-221X ] ; 2009-07.
English descriptors
- Teeft :
- Assay, Axon, Axon guidance, Bare branch morphology, Biol, Biol chem, Biology organization, Bottom face, Chick, Chick rgcs, Coloured, Concave face, Culture medium, Curr biol, Decorin, Dimer, Dimer interface, Dimerization, Dimerization interface, Disulphide bridges, Drosophila, Embo, Embo reports, Grenoble, Growth cones, Heparan, Heparan sulphate, Heparin, Human slit2, Hussain, Hydrogen bonds, Monomer, Morlot, Oligomers, Proc natl acad, Protein solution, Receptor, Rgcs, Robo, Seiradake, Slit2, Slit2 homodimerization domain, Sulfate, Sulphate, Supplementary information, Syndecan.
Abstract
Slit proteins are secreted ligands that interact with the Roundabout (Robo) receptors to provide important guidance cues in neuronal and vascular development. Slit–Robo signalling is mediated by an interaction between the second Slit domain and the first Robo domain, as well as being dependent on heparan sulphate. In an effort to understand the role of the other Slit domains in signalling, we determined the crystal structure of the fourth Slit2 domain (D4) and examined the effects of various Slit2 constructs on chick retinal ganglion cell axons. Slit2 D4 forms a homodimer using the conserved residues on its concave face, and can also bind to heparan sulphate. We observed that Slit2 D4 frequently results in growth cones with collapsed lamellipodia and that this effect can be inhibited by exogenously added heparan sulphate. Our results show that Slit2 D4–heparan sulphate binding contributes to a Slit–Robo signalling mechanism more intricate than previously thought.
Url:
DOI: 10.1038/embor.2009.95
Affiliations:
- Allemagne, France, Pays-Bas
- Auvergne-Rhône-Alpes, Bade-Wurtemberg, District de Karlsruhe, Rhône-Alpes
- Grenoble, Karlsruhe
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Mccarthy</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, 38042, Grenoble Cedex 9</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Unit of Virus Host‐Cell Interactions, UJF‐EMBL‐CNRS, UMR 5233, 6 rue Jules Horowitz, 38042, Grenoble Cedex 9</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">EMBO reports</title><title level="j" type="alt">EMBO REPORTS</title><idno type="ISSN">1469-221X</idno><idno type="eISSN">1469-3178</idno><imprint><biblScope unit="vol">10</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="736">736</biblScope><biblScope unit="page" to="741">741</biblScope><biblScope unit="page-count">6</biblScope><publisher>John Wiley & Sons, Ltd</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2009-07">2009-07</date></imprint><idno type="ISSN">1469-221X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1469-221X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Assay</term><term>Axon</term><term>Axon guidance</term><term>Bare branch morphology</term><term>Biol</term><term>Biol chem</term><term>Biology organization</term><term>Bottom face</term><term>Chick</term><term>Chick rgcs</term><term>Coloured</term><term>Concave face</term><term>Culture medium</term><term>Curr biol</term><term>Decorin</term><term>Dimer</term><term>Dimer interface</term><term>Dimerization</term><term>Dimerization interface</term><term>Disulphide bridges</term><term>Drosophila</term><term>Embo</term><term>Embo reports</term><term>Grenoble</term><term>Growth cones</term><term>Heparan</term><term>Heparan sulphate</term><term>Heparin</term><term>Human slit2</term><term>Hussain</term><term>Hydrogen bonds</term><term>Monomer</term><term>Morlot</term><term>Oligomers</term><term>Proc natl acad</term><term>Protein solution</term><term>Receptor</term><term>Rgcs</term><term>Robo</term><term>Seiradake</term><term>Slit2</term><term>Slit2 homodimerization domain</term><term>Sulfate</term><term>Sulphate</term><term>Supplementary information</term><term>Syndecan</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Slit proteins are secreted ligands that interact with the Roundabout (Robo) receptors to provide important guidance cues in neuronal and vascular development. Slit–Robo signalling is mediated by an interaction between the second Slit domain and the first Robo domain, as well as being dependent on heparan sulphate. In an effort to understand the role of the other Slit domains in signalling, we determined the crystal structure of the fourth Slit2 domain (D4) and examined the effects of various Slit2 constructs on chick retinal ganglion cell axons. Slit2 D4 forms a homodimer using the conserved residues on its concave face, and can also bind to heparan sulphate. We observed that Slit2 D4 frequently results in growth cones with collapsed lamellipodia and that this effect can be inhibited by exogenously added heparan sulphate. Our results show that Slit2 D4–heparan sulphate binding contributes to a Slit–Robo signalling mechanism more intricate than previously thought.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>Pays-Bas</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Bade-Wurtemberg</li><li>District de Karlsruhe</li><li>Rhône-Alpes</li></region><settlement><li>Grenoble</li><li>Karlsruhe</li></settlement></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Seiradake, Elena" sort="Seiradake, Elena" uniqKey="Seiradake E" first="Elena" last="Seiradake">Elena Seiradake</name></region><name sortKey="Cusack, Stephen" sort="Cusack, Stephen" uniqKey="Cusack S" first="Stephen" last="Cusack">Stephen Cusack</name><name sortKey="Cusack, Stephen" sort="Cusack, Stephen" uniqKey="Cusack S" first="Stephen" last="Cusack">Stephen Cusack</name><name sortKey="Henry, Maud" sort="Henry, Maud" uniqKey="Henry M" first="Maud" last="Henry">Maud Henry</name><name sortKey="Henry, Maud" sort="Henry, Maud" uniqKey="Henry M" first="Maud" last="Henry">Maud Henry</name><name sortKey="Jamin, Marc" sort="Jamin, Marc" uniqKey="Jamin M" first="Marc" last="Jamin">Marc Jamin</name><name sortKey="Lortat Acob, Hugues" sort="Lortat Acob, Hugues" uniqKey="Lortat Acob H" first="Hugues" last="Lortat-Jacob">Hugues Lortat-Jacob</name><name sortKey="Mccarthy, Andrew A" sort="Mccarthy, Andrew A" uniqKey="Mccarthy A" first="Andrew A" last="Mccarthy">Andrew A. Mccarthy</name><name sortKey="Mccarthy, Andrew A" sort="Mccarthy, Andrew A" uniqKey="Mccarthy A" first="Andrew A" last="Mccarthy">Andrew A. Mccarthy</name><name sortKey="Mccarthy, Andrew A" sort="Mccarthy, Andrew A" uniqKey="Mccarthy A" first="Andrew A" last="Mccarthy">Andrew A. Mccarthy</name><name sortKey="Seiradake, Elena" sort="Seiradake, Elena" uniqKey="Seiradake E" first="Elena" last="Seiradake">Elena Seiradake</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Von Philipsborn, Anne C" sort="Von Philipsborn, Anne C" uniqKey="Von Philipsborn A" first="Anne C" last="Von Philipsborn">Anne C. Von Philipsborn</name></region><name sortKey="Bastmeyer, Martin" sort="Bastmeyer, Martin" uniqKey="Bastmeyer M" first="Martin" last="Bastmeyer">Martin Bastmeyer</name><name sortKey="Fritz, Martin" sort="Fritz, Martin" uniqKey="Fritz M" first="Martin" last="Fritz">Martin Fritz</name></country><country name="Pays-Bas"><noRegion><name sortKey="Hemrika, Wieger" sort="Hemrika, Wieger" uniqKey="Hemrika W" first="Wieger" last="Hemrika">Wieger Hemrika</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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