Cargando…
Structure and functional relevance of the Slit2 homodimerization domain
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 he...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693880/ https://www.ncbi.nlm.nih.gov/pubmed/19498462 http://dx.doi.org/10.1038/embor.2009.95 |
_version_ | 1782168020446085120 |
---|---|
author | Seiradake, Elena von Philipsborn, Anne C Henry, Maud Fritz, Martin Lortat-Jacob, Hugues Jamin, Marc Hemrika, Wieger Bastmeyer, Martin Cusack, Stephen McCarthy, Andrew A |
author_facet | Seiradake, Elena von Philipsborn, Anne C Henry, Maud Fritz, Martin Lortat-Jacob, Hugues Jamin, Marc Hemrika, Wieger Bastmeyer, Martin Cusack, Stephen McCarthy, Andrew A |
author_sort | Seiradake, Elena |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2693880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-26938802009-06-12 Structure and functional relevance of the Slit2 homodimerization domain Seiradake, Elena von Philipsborn, Anne C Henry, Maud Fritz, Martin Lortat-Jacob, Hugues Jamin, Marc Hemrika, Wieger Bastmeyer, Martin Cusack, Stephen McCarthy, Andrew A EMBO Rep Scientific Report 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. Nature Publishing Group 2009-07 2009-06-05 /pmc/articles/PMC2693880/ /pubmed/19498462 http://dx.doi.org/10.1038/embor.2009.95 Text en Copyright © 2009, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission. |
spellingShingle | Scientific Report Seiradake, Elena von Philipsborn, Anne C Henry, Maud Fritz, Martin Lortat-Jacob, Hugues Jamin, Marc Hemrika, Wieger Bastmeyer, Martin Cusack, Stephen McCarthy, Andrew A Structure and functional relevance of the Slit2 homodimerization domain |
title | Structure and functional relevance of the Slit2 homodimerization domain |
title_full | Structure and functional relevance of the Slit2 homodimerization domain |
title_fullStr | Structure and functional relevance of the Slit2 homodimerization domain |
title_full_unstemmed | Structure and functional relevance of the Slit2 homodimerization domain |
title_short | Structure and functional relevance of the Slit2 homodimerization domain |
title_sort | structure and functional relevance of the slit2 homodimerization domain |
topic | Scientific Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693880/ https://www.ncbi.nlm.nih.gov/pubmed/19498462 http://dx.doi.org/10.1038/embor.2009.95 |
work_keys_str_mv | AT seiradakeelena structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT vonphilipsbornannec structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT henrymaud structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT fritzmartin structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT lortatjacobhugues structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT jaminmarc structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT hemrikawieger structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT bastmeyermartin structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT cusackstephen structureandfunctionalrelevanceoftheslit2homodimerizationdomain AT mccarthyandrewa structureandfunctionalrelevanceoftheslit2homodimerizationdomain |