Human-specific expression of Siglec-6 in the placenta

Els C M Brinkman-Van Der linden, Nancy Hurtado-Ziola, Toshiyuki Hayakawa, Lisa Wiggleton, Kurt Benirschke, Ajit Varki, Nissi Varki

Research output: Contribution to journalArticle

63 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)922-931
Number of pages10
JournalGlycobiology
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 1 2007
Externally publishedYes

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Sialic Acid Binding Immunoglobulin-like Lectins
Placenta
Leptin
Hominidae
Personnel
Ligands
Sialic Acids
Parturition
Aptitude
Trophoblasts
Lectins
Genetic Promoter Regions
Endometrium
Tyrosine
Glycoproteins
Cues
Transcription Factors
Cells
Availability

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Brinkman-Van Der linden, E. C. M., Hurtado-Ziola, N., Hayakawa, T., Wiggleton, L., Benirschke, K., Varki, A., & Varki, N. (2007). Human-specific expression of Siglec-6 in the placenta. Glycobiology, 17(9), 922-931. https://doi.org/10.1093/glycob/cwm065

Human-specific expression of Siglec-6 in the placenta. / Brinkman-Van Der linden, Els C M; Hurtado-Ziola, Nancy; Hayakawa, Toshiyuki; Wiggleton, Lisa; Benirschke, Kurt; Varki, Ajit; Varki, Nissi.

In: Glycobiology, Vol. 17, No. 9, 01.09.2007, p. 922-931.

Research output: Contribution to journalArticle

Brinkman-Van Der linden, ECM, Hurtado-Ziola, N, Hayakawa, T, Wiggleton, L, Benirschke, K, Varki, A & Varki, N 2007, 'Human-specific expression of Siglec-6 in the placenta', Glycobiology, vol. 17, no. 9, pp. 922-931. https://doi.org/10.1093/glycob/cwm065
Brinkman-Van Der linden ECM, Hurtado-Ziola N, Hayakawa T, Wiggleton L, Benirschke K, Varki A et al. Human-specific expression of Siglec-6 in the placenta. Glycobiology. 2007 Sep 1;17(9):922-931. https://doi.org/10.1093/glycob/cwm065
Brinkman-Van Der linden, Els C M ; Hurtado-Ziola, Nancy ; Hayakawa, Toshiyuki ; Wiggleton, Lisa ; Benirschke, Kurt ; Varki, Ajit ; Varki, Nissi. / Human-specific expression of Siglec-6 in the placenta. In: Glycobiology. 2007 ; Vol. 17, No. 9. pp. 922-931.
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