Loss of N-glycolylneuraminic acid in human evolution -: Implications for sialic acid recognition by siglecs

被引:127
作者
Brinkman-Van der Linden, ECM
Sjoberg, ER
Juneja, LR
Crocker, PR
Varki, N
Varki, A [1 ]
机构
[1] Univ Calif San Diego, Glycobiol Res & Training Ctr, CMM East, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[3] Cytel Inc, San Diego, CA 92093 USA
[4] Taiyo Kagaku Co, Yokaichi 510, Japan
[5] Univ Dundee, Dundee DD1 5EH, Scotland
关键词
D O I
10.1074/jbc.275.12.8633
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The common sialic acids of mammalian cells are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), Humans are an exception, because of a mutation in CMP-sialic acid hydroxylase, which occurred after our common ancestor with great apes, We asked if the resulting loss of Neu5Gc and increase in Neu5Ac in humans alters the biology of the siglecs, which are Ig superfamily members that recognize sialic acids. Human siglec-1 (sialoadhesin) strongly prefers Neu5Ac over Neu5Gc. Thus, humans have a higher density of siglec-1 ligands than great apes, Siglec-1-positive macrophages in humans are found primarily in the perifollicular zone, whereas in chimpanzees they also occur in the marginal zone and surrounding the periarteriolar lymphocyte sheaths. Although only a subset of chimpanzee macrophages express siglec-1, most human macrophages are positive. A known evolutionary difference is the strong preference of mouse siglec-2 (CD22) for Neu5Gc, contrasting with human siglec-2, which binds Neu5Ac equally well. To ask when the preference for Neu5Gc was adjusted in the human lineage, we cloned the first three extracellular domains of siglec-2 from all of the great apes and examined their preference. In fact, siglec-2 had evolved a higher degree of recognition flexibility before Neu5Gc was lost in humans. Human siglec-3 (CD33) and siglec-6 (obesity-binding protein 1) also recognize both Neu5Ac and Neu5Gc, and siglec-5 may have some preference for Neu5Gc, Others showed that siglec-4a (myelin-associated glycoprotein) prefers Neu5Ac over Neu5Gc, Thus, the human loss of Neu5Gc may alter biological processes involving siglec-1, and possibly, siglec-4a or -5.
引用
收藏
页码:8633 / 8640
页数:8
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