The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell migration.

Abstract	Delta1 acts as a membrane-bound ligand that interacts with the Notch receptor and plays a critical role in cell fate specification. By using peptide affinity chromatography followed by mass spectrometry, we have identified Dlg1 as a partner of the Delta1 C-terminal region. Dlg1 is a human homolog of the Drosophila Discs large tumor suppressor, a member of the membrane-associated guanylate kinase family of molecular scaffolds. We confirmed this interaction by co-immunoprecipitation experiments between endogenous Dlg1 and transduced Delta1 in a 3T3 cell line stably expressing Delta1. Moreover, we showed that deletion of a canonical C-terminal PDZ-binding motif (ATEV) in Delta1 abrogated this interaction. Delta4 also interacted with Dlg1, whereas Jagged1, another Notch ligand, did not. In HeLa cells, transfected Delta1 triggered the accumulation of endogenous Dlg1 at sites of cell-cell contact. Expression of Delta1 also reduced the motility of 3T3 cells. Finally, deletion of the ATEV motif totally abolished these effects but did not interfere with the ability of Delta1 to induce Notch signaling and T cell differentiation in co-culture experiments. These results point to a new, probably cell-autonomous function of Delta1, which is independent of its activity as a Notch ligand.
Authors	Emmanuelle M Six, Delphine Ndiaye, Guido Sauer, Yacine Laâbi, Rafika Athman, Ana Cumano, Christel Brou, Alain Israël, Frédérique Logeat
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 53 Pg. 55818-26 (Dec 31 2004) ISSN: 0021-9258 [Print] United States
PMID	15485825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing DLG1 protein, human Discs Large Homolog 1 Protein Dlg1 protein, mouse Intracellular Signaling Peptides and Proteins Ligands Membrane Proteins Proteins Receptors, Notch delta protein Green Fluorescent Proteins Guanylate Kinases
Topics	3T3 Cells Adaptor Proteins, Signal Transducing Amino Acid Motifs Amino Acid Sequence Animals Biotinylation Cell Communication Cell Differentiation Cell Line Cell Movement Discs Large Homolog 1 Protein Electrophoresis, Polyacrylamide Gel Flow Cytometry Green Fluorescent Proteins (metabolism) Guanylate Kinases HeLa Cells Hematopoietic Stem Cells (metabolism) Humans Immunoblotting Immunoprecipitation Intracellular Signaling Peptides and Proteins Ligands Mass Spectrometry Membrane Proteins (chemistry, metabolism, physiology) Mice Microscopy, Fluorescence Molecular Sequence Data Plasmids (metabolism) Protein Binding Protein Structure, Tertiary Proteins (chemistry, physiology) Receptors, Notch Sequence Homology, Amino Acid Transfection Wound Healing

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