Nutrient Responsive O-GlcNAcylation Dynamically Modulates Galectin 3 Secretion

ABSTRACT: Endomembrane glycosylation and cytoplasmic O-GlcNAcylation each play essential roles in nutrient sensing, and in fact, characteristic changes in glycan patterns have been described in disease states such as diabetes and cancer. These changes in glycosylation have important functional roles and can drive disease progression. However, little is known about the molecular mechanisms underlying how these signals are integrated and transduced into biological effects. Galectins are proteins that bind glycans and are secreted by a poorly characterized non-classical secretory mechanism. Once outside the cell, galectins bind to terminal galactose residues of cell surface glycans and modulate numerous extracellular functions like clathrin independent endocytosis (CIE). Originating in the cytoplasm, galectins are predicted substrates for O-GlcNAc addition and removal; and, as we have shown, galectin 3 is a substrate for OGT. This study also shows that galectin 3 secretion is sensitive to changes in O-GlcNAc levels. We determined that there is a significant difference in O-GlcNAcylation status between cytoplasmic and secreted galectin 3. We observed dramatic alterations in galectin 3 secretion in response to nutrient conditions and these changes were dependent on dynamic O-GlcNAcylation. Importantly, we showed that these O-GlcNAc driven alterations in galectin 3 secretion drove changes in CIE. These results indicate that dynamic O-GlcNAcylation of galectin 3 plays a role in modulating its secretion and can tune its function of transducing nutrient sensing information coded in cell surface glycosylation into biological effects.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hela Cell

SUBMITTER: Lara Abramowitz  

LAB HEAD: John Hanover

PROVIDER: PXD028139 | Pride | 2022-04-01

REPOSITORIES: Pride