Abstract
Siglecs (sialic acid-binding immunoglobulin-type lectins) are a family of immune regulatory receptors predominantly found on the cells of the hematopoietic system. A V-set Ig-like domain mediates the recognition of different sialylated glycoconjugates, which can lead to the activation or inhibition of the immune response, depending on the involved Siglecs. Siglecs are categorized into two subgroups: one including all CD33-related Siglecs and the other consisting of Siglec-1 (Sialoadhesin), Siglec-2 (CD22), Siglec-4 (myelin-associated glycoprotein, MAG) and Siglec-15. In contrast to the members of the CD33-related Siglecs, which share ∼50–99% sequence identity, Siglecs of the other subgroup show quite low homology (approximately 25–30% sequence identity). Based on the published sequences and functions of Siglecs, we performed phylogenetic analyses and sequence alignments to reveal the conservation of Siglecs throughout evolution. Therefore, we focused on the presence of Siglecs in different classes of vertebrates (fishes, amphibians, birds, reptiles and mammals), offering a bridge between the presence of different Siglecs and the biological situations of the selected animals.
Highlights
All eukaryotic cells are surrounded with proteoglycans, glycosphingolipids and glycoproteins that form an essential functional unit: the glycocalyx (Varki, 2017b)
sialic acid-binding immunoglobulin-like lectins (Siglecs) are categorized into two subgroups: one including all CD33-related Siglecs and the other consisting of Siglec-1 (Sialoadhesin), Siglec-2 (CD22), Siglec-4 and Siglec-15
In vitro studies have demonstrated that the interaction of Siglec-15 with DAP12 after sialic acid binding leads to a signalactivating osteoclast differentiation into their multinucleated states, which is responsible for bone resorption (Hiruma et al, 2011)
Summary
All eukaryotic cells are surrounded with proteoglycans, glycosphingolipids and glycoproteins that form an essential functional unit: the glycocalyx (Varki, 2017b). Sialic acids belong to the self-associated-molecular patterns (SAMPs), which are molecules that are recognized by inhibitory receptors in order to dampen immune reactions (Varki, 2011b; Varki, 2017a; b) Such modulations can be mediated via the interaction of sialic acid-binding immunoglobulin-like lectins (Siglecs) with distinct sialylated glycoconjugates (Crocker, 2005; Crocker et al, 2007; Pillai et al, 2012; Varki and Angata, 2006; Varki and Gagneux, 2012). The inhibitory Siglecs contain the so-called ‘immune receptor tyrosine-based inhibition motifs’ (ITIM) antagonizing the initiation of an immune reaction, which is mediated via the ‘immune receptor tyrosine-based activation motif’ (ITAM) (Crocker et al, 2007; Ravetch and Lanier, 2000). With the aim to contribute to the organization of the ever-growing number of complex immunoregulatory receptor families, we summarized the presence of Siglecs in several species by the performance of Blast searches and discuss the findings in the context of physiological changes throughout evolution (placenta types, lactation, and ecological niche/habitat)
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