Kempf, A, Boda, E, Kwok, JCF orcid.org/0000-0002-9798-9083 et al. (11 more authors) (2017) Control of cell shape, neurite outgrowth and migration by a novel Nogo-A/HSPG interaction. Developmental Cell, 43 (1). pp. 24-34. ISSN 1534-5807
Abstract
Heparan sulfate proteoglycans (HSPGs) critically modulate adhesion-, growth- and migration related processes. Here we show that the transmembrane protein Nogo-A inhibits neurite outgrowth and cell spreading in neurons and Nogo-A-responsive cell lines via HSPGs. The extracellular, active, 180 aa Nogo-A region called Nogo-A-Δ20 binds to heparin and brain derived heparan sulfate glycosaminoglycans (GAGs) but not to the closely related chondroitin sulfate GAGs. HSPGs are required for Nogo-A-Δ20-induced inhibition of adhesion, cell spreading, neurite outgrowth as well as for RhoA activation. Surprisingly, we show that Nogo-A-Δ20 can act via HSPGs independently of its receptor Sphingosine-1-Phosphate receptor 2 (S1PR2). We thereby identify a new functional binding receptor for Nogo-A-Δ20 and show that syndecan-3 and syndecan-4 are responsible for Nogo-A-Δ20-induced effects. Finally, we show in explant cultures ex vivo that Nogo-A-Δ20 promotes the migration of neuroblasts via HSPGs but not S1PR2.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier Inc. This is an author produced version of a paper published in Developmental Cell. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Nogo-A, HSPG, outgrowth, spreading, adhesion, neuroblast, migration, SVZ, RMS, syndecan |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Aug 2017 09:15 |
Last Modified: | 21 Sep 2018 00:38 |
Status: | Published |
Publisher: | Elsevier (Cell Press) |
Identification Number: | 10.1016/j.devcel.2017.08.014 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119723 |