| First Author | Dwyer CA | Year | 2012 |
| Journal | Neuroscience | Volume | 220 |
| Pages | 47-61 | PubMed ID | 22728091 |
| Mgi Jnum | J:192518 | Mgi Id | MGI:5465274 |
| Doi | 10.1016/j.neuroscience.2012.06.026 | Citation | Dwyer CA, et al. (2012) RPTPzeta/phosphacan is abnormally glycosylated in a model of muscle-eye-brain disease lacking functional POMGnT1. Neuroscience 220:47-61 |
| abstractText | Congenital muscular dystrophies (CMDs) with associated brain abnormalities are a group of disorders characterized by muscular dystrophy and brain and eye abnormalities that are frequently caused by mutations in known or putative glycotransferases involved in protein O-mannosyl glycosylation. Previous work identified alpha-dystroglycan as the major substrate for O-mannosylation and its altered glycosylation the major cause of these disorders. However, work from several labs indicated that other proteins in the brain are also O-mannosylated and therefore could contribute to CMD pathology in patients with mutations in the protein O-mannosylation pathway, however few of these proteins have been identified and fully characterized in CMDs. In this study we identify receptor protein tyrosine phosphatase zeta (RPTPzeta) and its secreted variant, phosphacan, as another potentially important substrate for protein O-mannosylation in the brain. Using a mouse model of muscle-eye-brain disease lacking functional protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1), we show that RPTPzeta/phosphacan is shifted to a lower molecular weight and distinct carbohydrate epitopes normally detected on the protein are either absent or substantially reduced, including Human Natural Killer-1 (HNK-1) reactivity. The spatial and temporal expression patterns of these O-mannosylated forms of RPTPzeta/phosphacan and its hypoglycosylation and loss of HNK-1 glycan epitopes in POMGnT1 knockouts are suggestive of a role in the neural phenotypes observed in patients and animal models of CMDs. |
