TY  - JOUR
AU  - Kempf, Anissa
AU  - Boda, Enrica
AU  - Kwok, Jessica C F
AU  - Fritz, Rafael
AU  - Grande, Valentina
AU  - Kaelin, Andrea M
AU  - Ristic, Zorica
AU  - Schmandke, Andre
AU  - Schmandke, Antonio
AU  - Tews, Bjoern
AU  - Fawcett, James W
AU  - Pertz, Olivier
AU  - Buffo, Annalisa
AU  - Schwab, Martin E
TI  - Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction.
JO  - Developmental cell
VL  - 43
IS  - 1
SN  - 1534-5807
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2017-05182
SP  - 24 - 34.e5
PY  - 2017
AB  - 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.
KW  - Carrier Proteins (NLM Chemicals)
KW  - Heparan Sulfate Proteoglycans (NLM Chemicals)
KW  - Nogo Proteins (NLM Chemicals)
KW  - Proteoglycans (NLM Chemicals)
KW  - Receptors, Lysosphingolipid (NLM Chemicals)
KW  - Heparitin Sulfate (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28943240
DO  - DOI:10.1016/j.devcel.2017.08.014
UR  - https://inrepo02.dkfz.de/record/129177
ER  -