Centrosomes: Til O-GlcNAc Do Us Apart

Abstract

The centrosome apparatus is vital for spindle assembly and chromosome segregation during mitotic divisions. Its replication, disjunction and separation have to be fine-tuned in space and time. A multitude of post-translational modifications (PTMs) have been implicated in centrosome modulation, including phosphorylation, ubiquitination and acetylation. Among them is the emerging O-linked N-acetylglucosamine (O-GlcNAc) modification. This quintessential PTM has a sole writer, O-GlcNAc transferase (OGT), and the only eraser, O-GlcNAcase (OGA). O-GlcNAc couples glucose metabolism with signal transduction and forms a yin-yang relationship with phosphorylation. Evidence from proteomic studies as well as single protein investigations has pinpointed a role of O-GlcNAc in centrosome number and separation, centriole number and distribution, as well as the cilia machinery emanating from the centrosomes. Herein we review our current understanding of the sweet modification embedded in centrosome dynamics and speculate that more molecular details will be unveiled in the future.

Spatial and temporal proteomics reveals the distinct distributions and dynamics of O-GlcNAcylated proteins

“…Cytoplasmic O-GlcNAcylated proteins are vital in cell homeostasis partly by modulating the functions of the mitochondrion ( Zhao et al, 2016 ) and centrosome ( Yuan et al, 2021 ). It was found that O-GlcNAcylation extensively stabilized proteins in these two organelles ( Figure 6E ).…”

Deciphering the Properties and Functions of Glycoproteins Using Quantitative Proteomics

“…Some mitochondrial proteins were reported to be O- GlcNAcylated, , and O- GlcNAcylated proteins in the mitochondrion had bidirectional changes in diabetes . Recently, it was found that O- GlcNAcylation modified proteins in the centrosome, the lysosome, and on the cell surface can regulate cell cycle, cancer progression, and cell–matrix interactions. − It is of great interest to use glycoproteomic strategies to systematically identify and quantify protein O- GlcNAcylation in these cellular compartments. Despite the technical difficulties to isolate these organelles, the proximity labeling methods, such as APEX, TurboID, and BioID, could accelerate the investigation of compartment-specific O- GlcNAcylation. − …”

Primary cilia and lipid raft dynamics

“…Multi-omics approaches, including lipidomics and glycomics, can also be used to identify novel components involved in the formation of primary cilia and lipid raft-mediated signalling. For example, O-linked β-N-acetylglycosaminylation (O-GlcNAcylation) is related to lipid raft-mediated Akt signalling [120,121] and ciliogenesis [122,123], and is associated with obesity, diabetes and cancer [124][125][126]. Modulation of O-GlcNAcylation may be a novel therapeutic approach to regulate lipid raft dynamics and primary cilia.…”