A basolateral sorting signal directs ADAM10 to adherens junctions and is required for its function in cell migration.
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.
Wild-Bode
Christine
C
Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany.
Fellerer
Katrin
K
Kugler
Johanna
J
Haass
Christian
C
Capell
Anja
A
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
D021382:Protein Sorting Signals; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D051722:ADAM Proteins