Pomgnt1, short for protein O-mannose β1,2-N-acetylglucosaminyltransferase 1, is a Golgi glycosyltransferase. It is crucial for the elongation of O-mannosyl glycans and catalyzes the formation of the N-acetylglucosamine (GlcNAc) β1→2Man linkage of O-mannosyl glycan [2,4]. Mutations in Pomgnt1 are mainly associated with muscle-eye-brain (MEB) disease, which is a type of α-dystroglycanopathy [1,3,6,7,8]. These diseases are characterized by defects in protein O-mannosylation and loss of the O-mannose-bound matriglycan on α-dystroglycan, reducing cell adhesion to the extracellular matrix [1].

Using POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient, studies have shown that POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion. This is due to an increased abundance of N-cadherin and site-specific changes in its N-glycan structures in the extracellular domain, which enhance homotypic interactions. Also, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated, triggering transcriptional changes comparable to the epithelial-mesenchymal transition (EMT) [1]. In glioblastoma, overexpression of PomGnT1 led to increased resistance to temozolomide, while knockdown decreased resistance, with PomGnT1 regulating factors in the epithelial-mesenchymal transition signaling [5].

In conclusion, Pomgnt1 is essential for O-mannosyl glycan elongation and has a significant impact on cell-cell adhesion and the EMT-related processes. Its deficiency can lead to MEB disease and other α-dystroglycanopathies. Studies using knockout cells have revealed important molecular mechanisms underlying these disease-related phenotypes, providing insights into the complex clinical symptoms of these conditions [1,5,6,7,8].