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

Autor:	Schmidt EN; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Lamprinaki D; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., McCord KA; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Joe M; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Sojitra M; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Waldow A; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Nguyen J; Department of Obstetrics & Gynaecology and Physiology University of Alberta, Edmonton, AB, Canada., Monyror J; Department of Pharmacology, University of Alberta, Edmonton, AB, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada., Kitova EN; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Mozaneh F; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Guo XY; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Jung J; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Enterina JR; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada., Daskhan GC; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Han L; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Krysler AR; Department of Pharmacology, University of Alberta, Edmonton, AB, Canada., Cromwell CR; Department of Pharmacology, University of Alberta, Edmonton, AB, Canada., Hubbard BP; Department of Pharmacology, University of Alberta, Edmonton, AB, Canada.; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada., West LJ; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.; Department of Surgery, University of Alberta, Edmonton, AB, Canada., Kulka M; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.; National Research Council, Edmonton, AB, Canada., Sipione S; Department of Pharmacology, University of Alberta, Edmonton, AB, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada., Klassen JS; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Derda R; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Lowary TL; Department of Chemistry, University of Alberta, Edmonton, AB, Canada.; Institute of Biological Chemistry, Academia Sinica, Nangang, Taipei, Taiwan.; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan., Mahal LK; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Riddell MR; Department of Obstetrics & Gynaecology and Physiology University of Alberta, Edmonton, AB, Canada., Macauley MS; Department of Chemistry, University of Alberta, Edmonton, AB, Canada. macauley@ualberta.ca.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada. macauley@ualberta.ca.; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada. macauley@ualberta.ca.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2023 Apr 22; Vol. 14 (1), pp. 2327. Date of Electronic Publication: 2023 Apr 22.
DOI:	10.1038/s41467-023-38030-6
Abstrakt:	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. (© 2023. The Author(s).)
Databáze:	MEDLINE
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