title: MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface.
abstract: Delta-Notch signaling plays an essential role in cell fate determination in many tissue types, including the central nervous system. Although the signaling mechanism of Notch has been extensively studied, the behaviors of its ligands are not well understood. In the present study, we found that, in the developing neural tube, Dll1(Delta-like 1) was mainly localized on the processes extending from nascent neurons toward both the pia and the ventricle and accumulated at apical termini, where adherens junctions (AJs) were formed. To understand the mechanism of Dll1 localization, we searched for binding proteins for Dll1 and identified a scaffolding molecule, MAGI1. In the developing spinal cord, MAGI1 mRNA was highly expressed in the ventricular zone, where Dll1 mRNA was expressed. MAGI1 protein accumulated at the AJs formed around the termini of apically extending processes and was partially colocalized with Dll1. MAGI1 bound not only to Dll1 but also to N-cadherin-beta-catenin complexes. In cultured AJ-forming fibroblasts, MAGI1 was localized at AJs, and Dll1 was recruited to these AJs through binding to MAGI1. In addition, Dll1 was stabilized on the cell surface by MAGI1. Taken together, these results suggest that Dll1 is presented on the surface of AJs formed at the apical termini of processes through interaction with MAGI1 to activate Notch on neighboring cells in the developing central nervous system.
authors.affiliation: KAN Research Institute Inc., 93 Chudoji-Awata-cho, Shimogyo-ku, Kyoto 600-8815, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Mizuhara
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Minaki
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ono
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D051528:Guanylate Kinases; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D009432:Neural Crest / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry; D017830:Octoxynol / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology; D013997:Time Factors; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496471:CNKSR3 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D018076:DNA, Complementary; D003902:Detergents; C502403:FAT1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; C064045:delta protein; C502406:fat1 protein, mouse; D017830:Octoxynol; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C493280:Magi1 protein, mouse