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Updated: Feb 22, 2026

Analyzing Murine Schwann Cell Development Along Growing Axons
Published on: November 21, 2012
Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction
Anissa Kempf1, Enrica Boda2, Jessica C F Kwok3
1Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, 8057 Zurich, Switzerland.
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.
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