POMT-dependent O -mannosylation regulates integrin β1 maturation via N -glycan processing

Protein O -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 protein O -mannosylation, as seen in POMT-deficient cells, on the maturation and function of integrin β1. We demonstrate that POMT deficiency interconnects with the N -glycosylation pathway, leading to an accumulation of immature oligomannose-type N -glycans and a corresponding decrease in complex-type N -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 impaired N -glycosylation and trafficking of integrin β1. Notably, the overexpression of MAN1B1 rescues the integrin β1 maturation defect, highlighting the interconnection between protein O -mannosylation and N -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.