Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily S0rge Kelm*, Andrea Pelz*, Roland Schauer*, Marie T. Filbint, Song Tangt, Maria-Elena de Bellardt, Ronald L. Schnaar t , James A. Mahoney t , Adele Hartnell § , Paul Bradfield § and Paul R. Crocker § *Biochemisches Institut II, University of Kiel, Olshausenstrage 40, 24098 Kiel, Germany. tDepartment of Biological Sciences, Hunter College of the City University of New York, New York 10021, USA. t Departments of Pharmacology and Neuroscience, The Johns Hopkir School of Medicine, Baltimore, Maryland 21205, USA. §Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. Background: Protein-carbohydrate interactions are believed to be important in many biological processes that involve cell-cell communication. Apart from the selectins, the only well-characterized vertebrate sialic acid-dependent adhesion molecules are CD22 and sialoadhesin; CD22 is a member of the immunoglobulin superfamily that is expressed by B lymphocytes and sialoadhesin is a macrophage receptor. The recent cloning of the gene encoding sialoadhesin has shown that it is also immunoglobulin-like. Both proteins share sequence similarity with the myelin-associated glycoprotein, an adhesion molecule of oligodendrocytes and Schwann cells that has been implicated in the process of myelination, raising the important question of whether myelin-asso- ciated glycoprotein is also a sialic acid-binding protein. Results: We have investigated the binding properties of these three receptors when expressed either in monkey COS cells or as chimaeric proteins containing the Fc portion of human immunoglobulin G. We demonstrate that, like sialoadhesin and CD22, myelin-associated glycoprotein mediates cell adhesion by binding to cell- surface glycans that contain sialic acid. We have dissected the specificities of these three adhesins further: whereas sialoadhesin binds equally to the sugar moieties NeuAccx2 -3Gal11 -3(4)GlcNAc or NeuAca2 - 3Gal 1 -3GalNAc, myelin-associated glycoprotein recognizes only NeuAccx2 -3Gal131-3GalNAc and CD22 binds specifically to NeuAcct2-6Gal1- 4GlcNAc. Furthermore, we show that the recognition of sialylated glycans on the surfaces of particular cell types leads to the selective binding of sialoadhesin to neutro- phils, myelin-associated glycoprotein to neurons and CD22 to lymphocytes. Conclusions: Our findings demonstrate that a subgroup of the immunoglobulin superfamily can mediate diverse biological processes through recognition of specific sialylated glycans on cell surfaces. We propose that this subgroup of proteins be called the sialoadhesin family. Current Biology 1994, 4:965-972 Background Cell adhesion molecules are essential in the development and maintenance of multicellular organisms. Most cell adhesion molecules belong to distinct, structurally re- lated families that include the immunoglobulin superfamily [1,2], integrins [3] and cadherins [4]. Members of these families are generally considered to mediate intercellular communication through specific protein-protein interactions. But the recent characteriza- tion of lectin-like cell adhesion molecules has shown that protein-carbohydrate interactions are also important in cellular communication [5]. Cell-surface carbohydrates are often terminated by sialic acids, a family of nine-carbon acidic sugars, all of which are derivatives of neuraminic acid (Fig. 1) [6]. Sialic acids contribute significantly to the variability of cell surfaces, as they occur mainly as terminal sugars in different link- ages bound to a variety of oligosaccharide glycans (for examples, see Table 1). Although N-acetylneuraminic acid (NeuAc) is the most abundant sialic acid, about 30 structural modifications of this sugar have been found in nature [6], increasing the variability of cell-surface carbo- hydrates even further. As the patterns of sialylated glycans are cell-type-dependent and developmentally regulated, it is likely that these sugars influence cellular communica- tion. Adhesion proteins that recognize specific sialylated glycans were, however, unknown until a few years ago, when the members of the selectin family were shown to Fig. 1. Structure of sialic acids. R 1 : acetyl in Neu5Ac or glycolyl in Neu5Gc. Correspondence to: Serge Kelm and Paul R. Crocker. © Current Biology 1994, Vol 4 No 11 I1 HO OR 3 I OH 965