N-Sulfated Heparan Sulfate Promotes Reelin Signaling as a Co-receptor.

ABSTRACT: Heparan sulfate (HS) plays a central role in signal transduction, while Reelin is an essential signaling protein in both the developing and adult brain. A Reelin COLBOS variant was recently discovered with enhanced HS binding and resilience against autosomal dominant Alzheimer's disease (ADAD), underscoring the importance of Reelin-HS interactions. However, the glycan determinants of Reelin-HS interactions have not been well-characterized, which we systematically investigated here. Surface plasmon resonance (SPR) showed that full length Reelin binds HS with high affinity (K_D = 17 ± 5 nM), which is enhanced by the COLBOS variant (K_D = 10 ± 2 nM). Competition SPR and glycan array studies further revealed that HS N-sulfation is critical for Reelin-HS bindin

SUBMITTER: Pan L 

PROVIDER: S-EPMC12781101 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature