title: A basolateral sorting signal directs ADAM10 to adherens junctions and is required for its function in cell migration.
abstract: ADAM10 (a disintegrin and metalloprotease) initiates regulated intramembrane proteolysis by shedding the ectodomain of a number of different substrates. Shedding is followed by subsequent intramembrane proteolysis leading to the liberation of intracellular domains capable of nuclear signaling. ADAM10 substrates have been found at cell-cell contacts and are apparently involved in cell-cell interaction and cell migration. Here we have investigated the cellular mechanism that guides ADAM10 to substrates at cell-cell contacts. We demonstrate that intracellular trafficking of ADAM10 critically requires a novel sorting signal within its cytoplasmic domain. Sequential deletion of the cytoplasmic domain and site-directed mutagenesis suggest that a potential Src homology 3-binding domain is essential for ADAM10 sorting. In a polarized epithelial cell line this motif not only targets ADAM10 to adherens junctions but is also strictly required for ADAM10 function in E-cadherin processing and cell migration.
authors.affiliation: Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wild-Bode
authors.forename: Katrin
authors.initials: K
authors.lastname: Fellerer
authors.forename: Johanna
authors.initials: J
authors.lastname: Kugler
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Anja
authors.initials: A
authors.lastname: Capell
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004285:Dogs; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics
chemical_list: D021382:Protein Sorting Signals; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D051722:ADAM Proteins