title: Mib1 modulates dynamin 2 recruitment via Snx18 to promote Dll1 endocytosis for efficient Notch signaling.
abstract: Notch signaling regulates normal development and tissue homeostasis. Ligand endocytosis plays critical roles in Notch signaling activation. Endocytic proteins such as epsin and dynamin participate in Notch ligand activity by mediating Notch ligand endocytosis. The ubiquitin ligase Mib1 also plays essential roles in Notch signaling via Notch ligand ubiquitination. However, the molecular links between Mib1 and endocytic proteins have not been fully defined. Here, we show that Mib1 is involved in dynamin 2 recruitment to Dll1 and that Snx18, which interacts with dynamin 2, modestly regulates Dll1 endocytosis. Furthermore, the ubiquitin ligase activity of Mib1 is induced by Notch ligand-receptor interactions. Mib1 promotes the interaction between dynamin 2 and Snx18 in an ubiquitin ligase activity-dependent manner. These results suggest that Mib1 modulates dynamin recruitment by regulating the interaction between Snx18 and dynamin 2, thereby helping to ensure the efficient signaling activity of Notch ligands.
authors.affiliation: Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Okano
authors.affiliation: Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Katsuto
authors.identifier: http://orcid.org/0000-0002-7685-6927
authors.initials: K
authors.lastname: Hozumi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
authors.forename: Saho
authors.initials: S
authors.lastname: Yoshioka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tonoki
authors.affiliation: Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan.|Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000818:Animals; D004705:Endocytosis; D006801:Humans; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D058305:Sorting Nexins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D051880:Receptors, Notch; D058305:Sorting Nexins; D044767:Ubiquitin-Protein Ligases