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PMID:17329366
| Citation |
Sasamura, T, Ishikawa, HO, Sasaki, N, Higashi, S, Kanai, M, Nakao, S, Ayukawa, T, Aigaki, T, Noda, K, Miyoshi, E, Taniguchi, N and Matsuno, K (2007) The O-fucosyltransferase O-fut1 is an extracellular component that is essential for the constitutive endocytic trafficking of Notch in Drosophila. Development 134:1347-56 |
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| Abstract |
Notch is a transmembrane receptor that mediates the cell-cell interactions necessary for many cell-fate decisions. Endocytic trafficking of Notch plays important roles in the activation and downregulation of this receptor. A Drosophila O-FucT-1 homolog, encoded by O-fut1, catalyzes the O-fucosylation of Notch, a modification essential for Notch signaling and ligand binding. It was recently proposed that O-fut1 acts as a chaperon for Notch in the endoplasmic reticulum and is required for Notch to exit the endoplasmic reticulum. Here, we report that O-fut1 has additional functions in the endocytic transportation of Notch. O-fut1 was indispensable for the constitutive transportation of Notch from the plasma membrane to the early endosome, which we show was independent of the O-fucosyltransferase activity of O-fut1. We also found that O-fut1 promoted the turnover of Notch, which consequently downregulated Notch signaling. O-fut1 formed a stable complex with the extracellular domain of Notch. In addition, O-fut1 protein added to conditioned medium and endocytosed was sufficient to rescue normal Notch transportation to the early endosome in O-fut1 knockdown cells. Thus, an extracellular interaction between Notch and O-fut1 is essential for the normal endocytic transportation of Notch. We propose that O-fut1 is the first example, except for ligands, of a molecule that is required extracellularly for receptor transportation by endocytosis. |
| Links |
PubMed Online version:10.1242/dev.02811 |
| Keywords |
Animals; Blotting, Western; Cells, Cultured; Drosophila/metabolism; Drosophila/physiology; Drosophila Proteins/metabolism; Extracellular Matrix Proteins/metabolism; Fucosyltransferases/metabolism; Gene Expression Regulation; Immunohistochemistry; Immunoprecipitation; Protein Transport/physiology; Receptors, Notch/metabolism; Signal Transduction/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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