Cited by 123Glycosylation and Glycoproteins ResearchReproductive System and PregnancyBlood groups and transfusion

Human-specific expression of Siglec-6 in the placenta

Brinkman-Van der Linden, E. C M, Hurtado-Ziola, N., Hayakawa, T., Wiggleton, L., Benirschke, K., Varki, A., Varki, N.·2007·Glycobiology

Abstract

CD33-related-Siglecs are lectins on immune cells that recognize sialic acids via extracellular domains, and deliver negative signals via cytosolic tyrosine-based regulatory motifs. We report that while Siglec-6/OB-BP1 (which can also bind leptin) is expressed on immune cells of both humans and the closely related great apes, placental trophoblast expression is human-specific, with little or no expression in ape placentae. Human-specific transcription factor recognition site changes in the Siglec-6 promoter region can help explain the human-specific expression. Human placenta also expresses natural ligands for Siglec-6 (a mixture of glycoproteins carrying cognate sialylated targets), in areas adjacent to Siglec-6 expression. Ligands were also found in uterine endometrium and on cell lines of trophoblastic or endometrial origin. Thus, Siglec-6 was recruited to placental expression during human evolution, presumably to interact with sialylated ligands for specific negative signaling functions and/or to regulate leptin availability. The control of human labor is poorly understood, but involves multiple cues, including placental signaling. Human birthing is also prolonged in comparison to that in our closest evolutionary relatives, the great apes. We found that Siglec-6 levels are generally low in placentae from elective surgical deliveries without known labor and the highest following completion of labor. We therefore speculate that the negative signaling potential of Siglec-6 was recruited to human-specific placental expression, to slow the tempo of the human birth process. The leptin-binding ability of Siglec-6 is also consistent with this hypothesis, as leptin-deficient mice have increased parturition times.

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Crossref · 10.1093/glycob/cwm065

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Authors
Brinkman-Van der Linden, E. C. M., Hurtado-Ziola, N., Hayakawa, T., Wiggleton, L., Benirschke, K., Varki, A., & Varki, N.
Affiliations
University of California San Diego (US)
Corresponding author
Varki, A.
Venue
Glycobiology
Published
2007-04-18
Volume
17
Issue
9
Pages
922-931
ISSN
  • 0959-6658 (ISSN-L)
  • 1460-2423
OpenAlex
W2164443274
Cited by
123
References
39
Citations by year
2026: 4 · 2025: 7 · 2024: 7 · 2023: 15 · 2022: 11 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 7 · 2013: 1 · 2012: 10
FWCI
2.49
Type
journal article
Language
en
Open access
closed
Locations
  • Glycobiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM032373)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
Keywords
Siglec-6, placenta, trophoblast, human evolution, great apes, sialic acid, leptin, negative signaling, transcription factor binding sites, endometrium, childbirth, labor duration
MeSH terms
Animals, Antibodies, Monoclonal, Base Sequence, Pan troglodytes, Cytosol, Humans, Molecular Sequence Data, Placenta, Species Specificity, Transcription, Genetic, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Gene Expression Regulation, Developmental, N-Acetylneuraminic Acid, 5' Untranslated Regions, Lectins, Mice, Sialic Acid Binding Ig-like Lectin 3

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