title: An evolutionary-conserved function of mammalian notch family members as cell adhesion molecules.
abstract: Notch family members were first identified as cell adhesion molecules by cell aggregation assays in Drosophila studies. However, they are generally recognized as signaling molecules, and it was unclear if their adhesion function was restricted to Drosophila. We previously demonstrated that a mouse Notch ligand, Delta-like 1 (Dll1) functioned as a cell adhesion molecule. We here investigated whether this adhesion function was conserved in the diversified mammalian Notch ligands consisted of two families, Delta-like (Dll1, Dll3 and Dll4) and Jagged (Jag1 and Jag2). The forced expression of mouse Dll1, Dll4, Jag1, and Jag2, but not Dll3, on stromal cells induced the rapid and enhanced adhesion of cultured mast cells (MCs). This was attributed to the binding of Notch1 and Notch2 on MCs to each Notch ligand on the stromal cells themselves, and not the activation of Notch signaling. Notch receptor-ligand binding strongly supported the tethering of MCs to stromal cells, the first step of cell adhesion. However, the Jag2-mediated adhesion of MCs was weaker and unlike other ligands appeared to require additional factor(s) in addition to the receptor-ligand binding. Taken together, these results demonstrated that the function of cell adhesion was conserved in mammalian as well as Drosophila Notch family members. Since Notch receptor-ligand interaction plays important roles in a broad spectrum of biological processes ranging from embryogenesis to disorders, our finding will provide a new perspective on these issues from the aspect of cell adhesion.
authors.affiliation: Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Murata
authors.affiliation: Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
authors.forename: Miya
authors.initials: M
authors.lastname: Yoshino
authors.affiliation: Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Hikosaka
authors.affiliation: Department of Hematology and Oncology, Division of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okuyama
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Corporate R&D Laboratories, Asahi Kasei Corporation, Fuji, Shizuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Sakano
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D051880:Receptors, Notch