Kempf, Anissa; Boda, Enrica; Kwok, Jessica C F; Fritz, Rafael; Grande, Valentina; Kaelin, Andrea M; Ristic, Zorica; Schmandke, Andre; Schmandke, Antonio; Tews, Bjoern; Fawcett, James W; Pertz, Olivier; Buffo, Annalisa; Schwab, Martin E (2017). Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction. Developmental cell, 43(1), 24-34.e5. Cell Press 10.1016/j.devcel.2017.08.014
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Biology > Institute of Cell Biology |
UniBE Contributor: |
Pertz, Olivier |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science |
ISSN: |
1534-5807 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Olivier Pertz |
Date Deposited: |
19 Feb 2018 15:28 |
Last Modified: |
05 Dec 2022 15:09 |
Publisher DOI: |
10.1016/j.devcel.2017.08.014 |
PubMed ID: |
28943240 |
Uncontrolled Keywords: |
HSPG RMS SVZ adhesion migration neuroblast nogo-A outgrowth spreading syndecan |
BORIS DOI: |
10.7892/boris.109215 |
URI: |
https://boris.unibe.ch/id/eprint/109215 |
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