Biological and biochemical analyses of Drosophilamutants lacking a novel O-GlcNAc modification

胞质和核蛋白的O-连接N-乙酰氨基葡萄糖(O-GlcNAc)修饰调节细胞的基本功能，参与糖尿病和神经退行性变的病因学。这种细胞内的O-GlcN酰化是由单一的O-GlcNAc转移酶OGT催化的。在这里，我们报道了一种新的OGT，EOGT，负责细胞外O-GlcN酰化。虽然OGT和EOGT都受氨基己糖的调节，但EOGT定位于内质网的管腔，并以非OGT的方式将GlcNAc转移到表皮生长因子样域。Eogt的缺失使表型类似于根尖细胞外基质缺陷引起的表型。DumPy是一种膜锚定的胞外蛋白，它是O-GlcN酰化的，EOGT是依赖DP的上皮细胞与基质相互作用所必需的。因此，分泌型和膜型糖蛋白的O-GlcN酰化是细胞表面细胞-细胞或细胞-基质相互作用的一种新的介体。

The O-linked- N -acetylglucosamine (O-GlcNAc) modifi cation of cytoplasmic and nuclear proteins regulates basic cellular functions and is involved in the aetiology of diabetes and neurodegeneration. This intracellular O-GlcNAcylation is catalyzed by a single O-GlcNAc transferase, OGT. Here we report a novel OGT, EOGT, responsible for extracellular O-GlcNAcylation. Although both OGT and EOGT are regulated by hexosamine fl ux, EOGT localizes to the lumen of the endoplasmic reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT-independent manner. Loss of Eogt gives phenotypes similar to those caused by defects in the apical extracellular matrix. Dumpy, a membrane-anchored extracellular protein, is O-GlcNAcylated, and EOGT is required for Dp-dependent epithelial cell - matrix interactions. Thus, O-GlcNAcylation of secreted and membrane glycoproteins is a novel mediator of cell - cell or cell - matrix interactions at the cell surface.