Human-specific expression of Siglec-6 in the placenta.
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.
Brinkman-Van der Linden
Els C M
EC
Glycobiology Research and Training Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0687, USA.
Hurtado-Ziola
Nancy
N
Hayakawa
Toshiyuki
T
Wiggleton
Lisa
L
Benirschke
Kurt
K
Varki
Ajit
A
Varki
Nissi
N
D020121:5' Untranslated Regions; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D003600:Cytosol / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D037102:Lectins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D002679:Pan troglodytes; D010920:Placenta / Q000378:metabolism*; D063268:Sialic Acid Binding Ig-like Lectin 3; D013045:Species Specificity; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; D037102:Lectins; C120775:SIGLEC6 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D019158:N-Acetylneuraminic Acid