Control of cell shape, neurite outgrowth, and migration by a Nogo-A/HSPG iInteraction
Summary 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...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
21 September 2017
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| In: |
Developmental cell
Year: 2017, Volume: 43, Issue: 1, Pages: 24-34 |
| ISSN: | 1878-1551 |
| DOI: | 10.1016/j.devcel.2017.08.014 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.devcel.2017.08.014 Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S1534580717306743 
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| Author Notes: | Anissa Kempf, Enrica Boda, Jessica C.F. Kwok, Rafael Fritz, Valentina Grande, Andrea M. Kaelin, Zorica Ristic, Andre Schmandke, Antonio Schmandke, Bjoern Tews, James W. Fawcett, Olivier Pertz, Annalisa Buffo, Martin E. Schwab |
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| 520 | |a Summary 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 amino acid Nogo-A region, named 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, and 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 the HSPG family members syndecan-3 and syndecan-4 as functional receptors for Nogo-A-Δ20. Finally, we show in explant cultures ex vivo that Nogo-A-Δ20 promotes the migration of neuroblasts via HSPGs but not S1PR2. | ||
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