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Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket

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DOIResolve DOI: https://doi.org/10.1038/s41467-023-38030-6
AuthorSearch for: ; Search for: ; Search for: ORCID identifier: https://orcid.org/0000-0001-6833-1509; Search for: ORCID identifier: https://orcid.org/0000-0003-0664-5275; Search for: ORCID identifier: https://orcid.org/0000-0002-7660-5490; Search for: ; Search for: ORCID identifier: https://orcid.org/0000-0003-0712-6987; Search for: ORCID identifier: https://orcid.org/0000-0002-6909-9147; Search for: ORCID identifier: https://orcid.org/0000-0003-0812-3286; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ORCID identifier: https://orcid.org/0000-0001-5549-0287; Search for: ORCID identifier: https://orcid.org/0000-0001-5147-1441; Search for: ORCID identifier: https://orcid.org/0000-0003-4353-9674; Search for: ORCID identifier: https://orcid.org/0000-0002-1990-3651; Search for: 1ORCID identifier: https://orcid.org/0000-0003-4741-9290; Search for: ; Search for: ; Search for: ORCID identifier: https://orcid.org/0000-0003-1365-6570; Search for: ORCID identifier: https://orcid.org/0000-0002-8331-8211; Search for: ORCID identifier: https://orcid.org/0000-0003-4791-8524; Search for: ORCID identifier: https://orcid.org/0000-0002-3203-2897; Search for: ORCID identifier: https://orcid.org/0000-0003-4579-1048
Affiliation
  1. National Research Council of Canada. Nanotechnology
FormatText, Article
Subjectglycobiology; glycoconjugates; glycolipids; nanoscale biophysics
Abstract
Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.
Publication date
PublisherSpringer Nature
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  • Nature Communications 14, no. 1, 2327 (12 April 2023): 1–17.
LanguageEnglish
Peer reviewedYes
NRC numberNRC-NANO-262
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Record identifier15cd70f1-9d55-4bcd-af22-ac91cd2dfbb6
Record created2023-07-05
Record modified2023-07-07
Date modified: