title: O-mannosylation: The other glycan player of ER quality control.
abstract: Nowhere else does the cell employ posttranslational protein modifications as extensively as in the endoplasmic reticulum (ER). In fact, such modifications can comprise the bulk of the mass of a mature protein in some cases. The most common modification is glycosylation, with N-linked glycans being the most commonly studied and best understood. However, the covalent modification of serine and threonine side chains with mannose or O-mannosylation has been gaining interest. Part of the attention comes from the realization that O-mannosylation is a conserved process found in most eukaryotes and defects in O-mannosylation can give rise to human disease. Long known to be important structural modification of some endomembrane system proteins, recent findings reveal that it is a common modification of unfolded proteins. For irreversibly misfolded proteins, O-mannosylation can aid in their disposal through ER or lysosomal pathways. The protein O-mannosylation pathway can also play an instrumental role in monitoring the folding of newly synthesized proteins. Proteins that fail to fold efficiently are O-mannosylated to remove them from harmful futile protein folding cycles and prepare them for disposal. Thus, O-mannosylation joins N-linked glycosylation as a major mechanism involved in the folding and quality control of newly synthesized proteins in the ER.
authors: Temasek Life Sciences Laboratory, National University of Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore.
authors: Chengchao
authors: C
authors: Xu
authors: Temasek Life Sciences Laboratory, National University of Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore. Electronic address: davis@tll.org.sg.
authors: Davis T W
authors: DT
authors: Ng
mesh_terms: D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D008364:Mannosyltransferases / Q000378:metabolism; D008954:Models, Biological; D011134:Polysaccharides / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D011134:Polysaccharides; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D008358:Mannose
keywords: ER associated degradation; ER stress; O-mannosylation; Protein folding; Protein glycosylation; Protein quality control