POMT-dependentO-mannosylation regulates integrin β1 maturation viaN-glycan processing

ProteinO-mannosylation is a critical post-translational modification that plays a pivotal role in the function of glycoproteins. The current study investigates the impact of defective proteinO-mannosylation, as seen in POMT-deficient cells, on the maturation and function of integrin β1. We demonstrate that POMT deficiency interconnects with theN-glycosylation pathway, leading to an accumulation of immature oligomannose-typeN-glycans and a corresponding decrease in complex-typeN-glycan structures. This glycosylation defect is associated with a significant reduction in the mature form of integrin β1 on the cell surface, which is crucial for integrin-mediated signaling and cell adhesion. Most interestingly, the downregulation of the α-mannosidase MAN1B1 in POMT-deficient cells contributes to the impairedN-glycosylation and trafficking of integrin β1. Notably, the overexpression of MAN1B1 rescues the integrin β1 maturation defect, highlighting the interconnection between proteinO-mannosylation andN-glycosylation pathways. Our findings significantly contribute to the understanding of the molecular mechanisms underlying POMT-related disorders and provide novel insights that could guide future research and therapeutic strategies.