First Author | Kempf A | Year | 2017 |
Journal | Dev Cell | Volume | 43 |
Issue | 1 | Pages | 24-34.e5 |
PubMed ID | 28943240 | Mgi Jnum | J:245874 |
Mgi Id | MGI:5918018 | Doi | 10.1016/j.devcel.2017.08.014 |
Citation | Kempf A, et al. (2017) Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction. Dev Cell 43(1):24-34.e5 |
abstractText | 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-Delta20, 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-Delta20-induced inhibition of adhesion, cell spreading, and neurite outgrowth, as well as for RhoA activation. Surprisingly, we show that Nogo-A-Delta20 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-Delta20. Finally, we show in explant cultures ex vivo that Nogo-A-Delta20 promotes the migration of neuroblasts via HSPGs but not S1PR2. |