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Development ePress online publication date 28 Feb 2007
doi: 10.1242/dev.02811
Research article
The O-fucosyltransferase O-fut1 is an extracellular component that is essential for the constitutive endocytic trafficking of Notch in Drosophila
Takeshi Sasamura,
Hiroyuki O. Ishikawa,
Nobuo Sasaki,
Syunsuke Higashi,
Maiko Kanai,
Shiho Nakao,
Tomonori Ayukawa,
Toshiro Aigaki,
Katsuhisa Noda,
Eiji Miyoshi,
Naoyuki Taniguchi,
and
Kenji Matsuno*
* Author for correspondence (e-mail: matsuno{at}rs.noda.tus.ac.jp)
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.
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© The Company of Biologists Ltd 2007
