Siglecs: A journey through the evolution of sialic acid-binding immunoglobulin-type lectins

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.

Characterization of Sialic Acid-Binding Immunoglobulin-Type Lectins in Fish Reveals Teleost-Specific Structures and Expression Patterns

“…Lehmann et al suggested that these motifs are involved in signal transduction and contribute to biological functions different from those described for mammalian MAG [16]. Furthermore, our previous sequence analysis [15] confirmed the presence of ITIMs in coelacanth, while almost all investigated higher vertebrates were ITIM-negative. Consequently, the ITIM motif seems to be an ancestral feature that has persisted in most Siglecs but was lost during the evolution of higher vertebrates [15,16].…”

“…The expression of MAG is restricted to Schwann cells and oligodendrocytes. The dimerization of MAG is essential for specific axon-myelin spacing (9-12 nm) and strongly depends on the glycosylation pattern of MAG [15,35,54,55]. Therefore, we also inspected potential N-glycosylation sites of the MAG sequences from maraena whitefish and Atlantic salmon.…”

“…To date, fifteen and nine Siglecs have been identified in human and mouse, respectively, each expressed by defined cell types and responding to a particular set of ligands [12][13][14]. Remarkably, Siglec1, CD22, MAG, and Siglec15 were already present in the animal kingdom before the separation of tetrapods and teleost fishes more than 400 million years ago [15]. However, little is known about the physiological role of Siglecs in teleosts [16,17] including their tissue-specific basal expression profiles.…”

Maximum reproductive lifespan correlates with CD33rSIGLEC gene number: Implications for NADPH oxidase‐derived reactive oxygen species in aging

“…Control of neutrophil ROS production is at least partly mediated by CD33-related subfamily of Siglecs (Sialic acid-binding Ig-like lectins) 28,[32][33][34][35][36][37][38][39] encoded in the CD33rSIGLEC gene cluster, and referred to as CD33rSiglecs. [40][41][42][43][44] Consistent with the phylogenetic distribution of sialic acids in the deuterostome lineage of animals, this gene cluster only occurs vertebrates. The CD33rSiglecs recognize endogenous sialylated glycans as SAMPs 29 and modulate myeloid cell lineage reactivity.…”

Sialic acid and biology of life: An introduction

“…Siglecs include (a) CD33-related Siglecs and (b) Siglec-1 (Sialoadhesin), Siglec-2 (CD22), Siglec-4 (myelin-associated glycoprotein, MAG), and Siglec-15. Phylogenetic studies in higher vertebrates including fishes, amphibians, birds, reptiles and mammals have revealed that Siglecs are conserved in evolution [316]. A loss of Siglec genes in rodents have been reported.…”