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Protein-<jats:italic>O<\/jats:italic>-mannosyl transferase 1 (POMT1) is the first enzyme required for the glycosylation of \u03b1-dystroglycan, and mutations in the POMT1 gene can lead to both Walker-Warburg syndrome (WWS) and limb girdle muscular dystrophy type 2K (LGMD2K). WWS is associated with severe mental retardation and major structural abnormalities in the brain; however, LGMD2K patients display a more mild retardation with no obvious structural defects in the brain. In a screen for synaptic mutants in<jats:italic>Drosophila<\/jats:italic>, we identified mutations in the<jats:italic>Drosophila<\/jats:italic>ortholog of POMT1,<jats:italic>dPOMT1<\/jats:italic>. Because synaptic defects are a plausible cause of mental retardation, we investigated the molecular and physiological defects associated with loss of<jats:italic>dPOMT1<\/jats:italic>in<jats:italic>Drosophila<\/jats:italic>. In<jats:italic>dPOMT1<\/jats:italic>mutants, there is a decrease in the efficacy of synaptic transmission and a change in the subunit composition of the postsynaptic glutamate receptors at the neuromuscular junction. We demonstrate that dPOMT1 is required to glycosylate the<jats:italic>Drosophila<\/jats:italic>dystroglycan ortholog<jats:italic>Dg in vivo<\/jats:italic>, and that this is the likely cause of these synaptic defects because (1) mutations in<jats:italic>Dg<\/jats:italic>lead to similar synaptic defects and (2) genetic interaction studies suggest that<jats:italic>dPOMT1<\/jats:italic>and<jats:italic>Dg<\/jats:italic>function in the same pathway. These results are consistent with the model that<jats:italic>dPOMT1<\/jats:italic>-dependent glycosylation of Dg is necessary for proper synaptic function and raise the possibility that similar synaptic defects occur in the congenital muscular dystrophies.<\/jats:p>","DOI":"10.1523\/jneurosci.0478-08.2008","type":"journal-article","created":{"date-parts":[[2008,4,2]],"date-time":"2008-04-02T16:34:29Z","timestamp":1207154069000},"page":"3781-3789","source":"Crossref","is-referenced-by-count":58,"title":["Synaptic Defects in a<i>Drosophila<\/i>Model of Congenital Muscular Dystrophy"],"prefix":"10.1523","volume":"28","author":[{"given":"Yogesh P.","family":"Wairkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee G.","family":"Fradkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasprina 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