1. Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction
- Author
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Anissa Kempf, Rafael D. Fritz, Zorica Ristic, Martin E. Schwab, Antonio Schmandke, Andrea M Kaelin, Valentina Grande, Enrica Boda, Jessica C. F. Kwok, James W. Fawcett, Annalisa Buffo, Olivier Pertz, Bjoern Tews, Andre Schmandke, University of Zurich, Kempf, Anissa, Fawcett, James [0000-0002-7990-4568], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Nogo Proteins ,RHOA ,migration ,Syndecan 1 ,1309 Developmental Biology ,1307 Cell Biology ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Cell Movement ,Receptor ,Cells, Cultured ,S1PR2 ,biology ,Heparan sulfate ,adhesion ,HSPG ,neuroblast ,nogo-A ,outgrowth ,RMS ,spreading ,SVZ ,syndecan ,Cell biology ,Receptors, Lysosphingolipid ,Proteoglycans ,psychological phenomena and processes ,Protein Binding ,Neurite ,Neuronal Outgrowth ,610 Medicine & health ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,1300 General Biochemistry, Genetics and Molecular Biology ,mental disorders ,1312 Molecular Biology ,Neurites ,Animals ,Chondroitin sulfate ,Molecular Biology ,Cell Shape ,10242 Brain Research Institute ,Cell Biology ,500 Science ,carbohydrates (lipids) ,030104 developmental biology ,chemistry ,biology.protein ,570 Life sciences ,Heparitin Sulfate ,Carrier Proteins ,030217 neurology & neurosurgery ,Heparan Sulfate Proteoglycans ,Developmental Biology - 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 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.
- Published
- 2017
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