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Uniquely human changes in expression and binding specificity of Siglec‐11: implications for human brain evolution (787.2)
Author(s) -
Schwarz Flavio,
Deng Lingquan,
Landig Corinna,
Varki Nissi,
Varki Ajit
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.787.2
Subject(s) - siglec , sialic acid , cd22 , glycan , microglia , human brain , biology , pseudogene , glycomics , biochemistry , gene , chemistry , antibody , microbiology and biotechnology , glycoprotein , genetics , monoclonal antibody , immunology , neuroscience , inflammation , genome
We are exploring the role of Siglec‐11, a member of the sialic acid‐recognizing immunoglobulin‐like lectin family, in the modulation of microglial functions in the human brain. Human SIGLEC11 underwent two tandem and likely simultaneous gene conversions by the adjacent pseudogene SIGLEC16P (Wang et al ., Mol. Biol. Evol. , 29:2073‐2086, 2012). These genes conversions preserved an intact open reading frame, but changed 5' untranslated sequences, likely altering transcription of SIGLEC11 . Using specific antibodies, we confirmed the resulting uniquely human expression of Siglec‐11 in brain microglia, and next wished to define its ligands. Surprisingly, we did not observe robust binding of human Siglec‐11 to any sialic acid‐containing glycan in multiple assay platforms. In contrast chimpanzee Siglec‐11 strongly recognized several glycans terminating with sialic acid, with a preference for the non‐human sialic acid N ‐glycolylneuraminic acid (Neu5Gc). Accordingly, chimp Siglec‐11 bound to cells proportionally to their Neu5Gc content, but human Siglec‐11 exhibited minimal binding to the same cells. We also found that human Siglec‐11 binds to a microglial cell line independently of sialic acid, and are characterizing the nature of this ligand. Alterations in the expression pattern and ligand‐binding specificity of human Siglec‐11 may have evolved to generate novel, human‐specific functions in the brain. Grant Funding Source : Supported by P01 HL057345