Pomgnt1, also known as protein O-mannose β1,2-N-acetylglucosaminyltransferase 1, is a Golgi glycosyltransferase crucial for the elongation of O-mannosyl glycans. It catalyzes the formation of the N-acetylglucosamine (GlcNAc) β1→2Man linkage of O-mannosyl glycan. Its function is essential in the context of protein O-mannosylation, which is involved in maintaining cell-extracellular matrix adhesion. Mutations in Pomgnt1 are mainly associated with muscle-eye-brain (MEB) disease, a type of α-dystroglycanopathy [1,2,3,4,5,6].

Using Pomgnt1 knockout HEK293T cells and fibroblasts from an MEB patient, research has 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. Additionally, in Pomgnt1-deficient cells, ERK1/2 and p38 signaling pathways are activated, and transcriptional changes similar to the epithelial-mesenchymal transition (EMT) are triggered [1].

In conclusion, Pomgnt1 is vital for the elongation of O-mannosyl glycans and normal cell-extracellular matrix adhesion. The study of Pomgnt1-deficient models has provided insights into the molecular mechanisms underlying MEB disease, suggesting that changes in cadherin-mediated cell-cell adhesion and EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general [1].

References:

1. Noor, Sina Ibne, Hoffmann, Marcus, Rinis, Natalie, Rapp, Erdmann, Strahl, Sabine. 2021. Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion. In The Journal of biological chemistry, 296, 100433. doi:10.1016/j.jbc.2021.100433. https://pubmed.ncbi.nlm.nih.gov/33610554/

2. Yamamoto, Tomoko, Kato, Yoichiro, Kawaguchi, Motoko, Shibata, Noriyuki, Kobayashi, Makio. . Expression and localization of fukutin, POMGnT1, and POMT1 in the central nervous system: consideration for functions of fukutin. In Medical electron microscopy : official journal of the Clinical Electron Microscopy Society of Japan, 37, 200-7. doi:. https://pubmed.ncbi.nlm.nih.gov/15614444/

3. Manya, Hiroshi, Kuwabara, Naoyuki, Kato, Ryuichi, Endo, Tamao. . FAM3B/PANDER-Like Carbohydrate-Binding Domain in a Glycosyltransferase, POMGNT1. In Methods in molecular biology (Clifton, N.J.), 2132, 609-619. doi:10.1007/978-1-0716-0430-4_52. https://pubmed.ncbi.nlm.nih.gov/32306360/

4. Jiao, Hui, Manya, Hiroshi, Wang, Shuo, Wu, Xiru, Xiong, Hui. 2013. Novel POMGnT1 mutations cause muscle-eye-brain disease in Chinese patients. In Molecular genetics and genomics : MGG, 288, 297-308. doi:10.1007/s00438-013-0749-5. https://pubmed.ncbi.nlm.nih.gov/23689641/

5. Song, Danyu, Dai, Yi, Chen, Xiaoyu, Toda, Tatsushi, Xiong, Hui. 2021. Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients. In Clinical genetics, 99, 384-395. doi:10.1111/cge.13886. https://pubmed.ncbi.nlm.nih.gov/33200426/

6. Liu, Yi-Dan, Tan, Dan-Dan, Song, Dan-Yu, Wei, Wei, Xiong, Hui. 2023. Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease. In Frontiers in genetics, 14, 1170089. doi:10.3389/fgene.2023.1170089. https://pubmed.ncbi.nlm.nih.gov/37342771/