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.
Pharmacology, Toxicology and Pharmaceutical Science
1
1%
Other
2
3%
Unknown
27
36%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 August 2021.
All research outputs
#16,722,153
of 26,827,235 outputs
Outputs from Developmental Cell
#3,429
of 4,481 outputs
Outputs of similar age
#184,143
of 330,398 outputs
Outputs of similar age from Developmental Cell
#61
of 80 outputs
Altmetric has tracked 26,827,235 research outputs across all sources so far. This one is in the 36th percentile – i.e., 36% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 80 others from the same source and published within six weeks on either side of this one. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
