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Protein interactors of 3-O sulfated heparan sulfates in human MCI and age-matched control cerebrospinal fluid

ABSTRACT: Heparan (HS) proteoglycans (HSPGs) are common on the cell surface and mediate many physiological processes. Binding of HSPG ligands is determined by the sulfation code on the heparan sulfate chain and the HS chain can be N-/2-O/6-O- or 3-O-sulfated, generating a heterogenous sulfation pattern. 3-O sulfated HS (3S-HS) have been reported to play a role in several pathological processes such as the coagulation system, viral pathogenesis, or in the binding and internalization of tau in Alzheimer’s disease. Few 3S-HS-specific interactors are known and the role of 3S-HS in health and disease is limited, especially in the central nervous system. Using human CSF as a surrogate for the extracellular compartment of the CNS, we determined the interactome of synthetic heparan sulfate oligosaccharides with defined sulfation patterns. These AE-MS studies significantly expand the proteins that can interact with HS and for which 3O sulfation is required. LRP1 was found as a novel 3S-HS interactor, requiring GlcA-GlcNS6S3S for binding, similar to ATIII. Both interactions were validated via Western blot. Our dataset brings forward new HS and 3S-HS ligands which can be pertinent to unravel molecular mechanisms dependent on 3S-HS in (patho)physiological conditions.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Alzheimer's Disease

SUBMITTER: An Staes

LAB HEAD: Kris Gevaert

PROVIDER: PXD034935 | Pride | 2022-08-09

REPOSITORIES: Pride

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