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1 Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
2 PRESTO, JST, 4-1-8 Honcho, Kawaguchi, Saitama, Japan
3 Genome and Drug Research Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
4 Genetic Strains Research Center, National Institute of Genetics, 1111 Mishima, Shizuoka 411-8540, Japan
5 Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Notch (N) and its ligands, Delta (Dl) and Serrate (Ser), are transmembrane proteins that mediate the cellcell interactions necessary for many cell-fate decisions. In Drosophila, N is predominantly localized to the apical portion of epithelial cells, but the mechanisms and functions of this localization are unknown. Here, we found N, Dl, and Ser were mostly located in the region from the subapical complex (SAC) to the apical portion of the adherens junctions (AJs) in wing disc epithelium. N was delivered to the SAC/AJs in two phases. First, polarized exocytosis specifically delivered nascent N to the apical plasma membrane and AJs in an O-fut1-independent manner. Second, N at the plasma membrane was relocated to the SAC/AJs by Dynamin- and Rab5-dependent transcytosis; this step required the O-fut1 function. Disruption of the apical polarity by Drosophila E-cadherin (DEcad) knock down caused N and Dl localization to the SAC/AJs to fail. N, but not Dl, formed a specific complex with DEcad in vivo. Finally, our results suggest that juxtacrine signaling in epithelia generally depends on the apicobasally polarized structure of epithelial cells.
* Correspondence: E-mail: matsuno{at}rs.noda.tus.ac.jp
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