Evolution of Mincle in vertebrates: adaptation to environmental stresses

Innate immune receptors serve as the first line of defense against pathogens. C-type lectin receptors (CLRs) are a group of innate immune receptors that recognize a variety of ligands, including glycans, glycolipids, proteins, and insoluble crystals. One such CLR is Mincle (Macrophage-inducible C-type lectin), which can recognize foreign or normally sequestered endogenous glycolipids. Therefore, Mincle is both an essential receptor for recognizing pathogens and a sensor for endogenous molecules. While the functions of Mincle have been characterized, how Mincle may have evolved, and which ligands are recognized at each evolutionary stage remain unknown. In mammals, Mincle is known to be conserved, especially in the domains that bind the sugar moieties of glycolipid ligands. Recently, the sequence and structure of a putative Mincle in fish were investigated relative to mammalian Mincle in order to gain an understanding of changes in the binding domains that occurred as vertebrates adapted to terrestrial environments. In this review, we will first describe the identity and binding mode of glycolipid ligands for mammalian Mincle. Then their similarities and differences between putative fish Mincle will be discussed to get an insight into how the scope of recognized ligands changed, and which pressures drove the evolution of this receptor. • Mincle binds foreign and stress-exposed self-glycolipids to maintain homeostasis. • In fish, Mincle favors binding monosaccharides from ligands, like self glycolipids. • Binding pocket may have enlarged in vertebrates to permit disaccharide glycolipids. • Terrestrialization may have driven Mincle adaption to the microbe environments.