spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 28 February 2007
doi: 10.1242/dev.02811

Development 134, 1347-1356 (2007)
Published by The Company of Biologists 2007
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.02811v1
134/7/1347    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sasamura, T.
Right arrow Articles by Matsuno, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sasamura, T.
Right arrow Articles by Matsuno, K.

The O-fucosyltransferase O-fut1 is an extracellular component that is essential for the constitutive endocytic trafficking of Notch in Drosophila

Takeshi Sasamura1,2, Hiroyuki O. Ishikawa3, Nobuo Sasaki2, Syunsuke Higashi2, Maiko Kanai1,2, Shiho Nakao2, Tomonori Ayukawa2, Toshiro Aigaki4, Katsuhisa Noda5, Eiji Miyoshi5, Naoyuki Taniguchi5 and Kenji Matsuno1,2,3,*

1 Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama, Japan.
2 Department of Biological Science and Technology, Tokyo University of Science, Chiba 278-8510, Japan.
3 Genome and Drug Research Center, Tokyo University of Science, Chiba 278-8510, Japan.
4 Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
5 Department of Biochemistry, Osaka University, Graduate School of Medicine, Osaka 565-0871, Japan.

* Author for correspondence (e-mail: matsuno{at}rs.noda.tus.ac.jp)

Accepted 17 January 2007

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.

Key words: Notch, O-fucosyltransferase, O-fut1, Endocytosis, Drosophila




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. Stahl, K. Uemura, C. Ge, S. Shi, Y. Tashima, and P. Stanley
Roles of Pofut1 and O-Fucose in Mammalian Notch Signaling
J. Biol. Chem., May 16, 2008; 283(20): 13638 - 13651.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2007