Publication – Dissecting the abilities of murine Siglecs to interact with gangliosides

Excited to share the work that Eddie has recently published in The Journal of Biological Chemistry.

Dissecting the abilities of murine Siglecs to interact with gangliosides,
Journal of Biological Chemistry,
Edward N. Schmidt, Xue Yan Guo, Duong T. Bui, Jaesoo Jung, John S. Klassen, Matthew S. Macauley,
2024, 107482, ISSN 0021-9258, https://doi.org/10.1016/j.jbc.2024.107482.

Read the full article here.

Siglecs are cell surface receptors whose functions are tied to the binding of their sialoglycan ligands. Recently, we developed an optimized liposome formulation and used it to investigate the binding of human Siglecs (hSiglec) against a panel of gangliosides. Animal models, more specifically murine models, are used to understand human biology, however, species-specific differences can complicate the interpretation of the results. Herein, we used our optimized liposome formulation to dissect the interactions between murine Siglecs (mSiglecs) and gangliosides to assess the appropriateness of mSiglecs as a proxy to better understand the biological roles of hSiglec-ganglioside interactions. Using our optimized liposome formulation, we found that ganglioside binding is generally conserved between mice and humans with mSiglec-1, -E, -F, and -15 binding multiple gangliosides like their human counterparts. However, in contrast to the hSiglecs, we observed little to no binding between the mSiglecs and ganglioside GM1a. Detailed analysis of mSiglec-1 interacting with GM1a and its structural isomer, GM1b, suggests that mSiglec-1 preferentially binds α2-3-linked sialic acids presented from the terminal galactose residue. The ability of mSiglecs to interact or not interact with gangliosides, particularly GM1a, has implications for using mice to study neurodegenerative diseases, infections, and cancer, where interactions between Siglecs and glycolipids have been proposed to modulate these human diseases.

Territorial Acknowledgement

The University of Alberta, its buildings, labs, and research stations are primarily located on the traditional territory of Cree, Blackfoot, Métis, Nakota Sioux, Iroquois, Dene, and Ojibway/Saulteaux/Anishinaabe nations; lands that are now known as part of Treaties 6, 7, and 8 and homeland of the Métis. The University of Alberta respects the sovereignty, lands, histories, languages, knowledge systems, and cultures of First Nations, Métis and Inuit nations.

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