Protein O-mannosylation across kingdoms and related diseases: From glycobiology to glycopathology

Abstract

The post-translational glycosylation of proteins by O-linked α-mannose is conserved from bacteria to humans. Due to advances in high-throughput mass spectrometry-based approaches, a variety of glycoproteins are identified to be O-mannosylated. Various proteins with O-mannosylation are involved in biological processes, providing essential necessity for proper growth and development. In this review, we summarize the process and regulation of O-mannosylation. The multi-step O-mannosylation procedures are quite dynamic and complex, especially when considering the structural and functional inspection of the involved enzymes. The widely studied O-mannosylated proteins in human include α-Dystroglycan (α-DG), cadherins, protocadherins, and plexin, and their aberrant O-mannosylation are associated with many diseases. In addition, O-mannosylation also contributes to diverse functions in lower eukaryotes and prokaryotes. Finally, we present the relationship between O-mannosylation and gut microbiota (GM), and elucidate that O-mannosylation in microbiome is of great importance in the dynamic balance of GM. Our study provides an overview of the processes of O-mannosylation in mammalian cells and other organisms, and also associated regulated enzymes and biological functions, which could contribute to the understanding of newly discovered O-mannosylated glycoproteins.

Keywords: ER-associated protein degradation; Enzyme structure; Gut microbiota; Mannosyltransferase; O-mannosylation.