Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-6-27
pubmed:abstractText
We report that during cortical development in the mouse embryo, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) critically regulates Notch signaling by antagonizing the ectodomain shedding of Notch ligands, which is mediated by a disintegrin and metalloproteinase domain 10 (ADAM10). In the embryonic brain, RECK is specifically expressed in Nestin-positive neural precursor cells (NPCs). Reck-deficient NPCs undergo precocious differentiation that is associated with downregulated Nestin expression, impaired Notch signaling and defective self-renewal. These phenotypes were substantially rescued either by enhancing Notch signaling or by suppressing endogenous ADAM10 activity. Consequently, we found that RECK regulates the ectodomain shedding of Notch ligands by directly inhibiting the proteolytic activity of ADAM10. This mechanism appeared to be essential for Notch ligands to properly induce Notch signaling in neighboring cells. These findings indicate that RECK is a physiological inhibitor of ADAM10, an upstream regulator of Notch signaling and a critical modulator of brain development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-6256
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
838-45
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17558399-ADAM Proteins, pubmed-meshheading:17558399-Amyloid Precursor Protein Secretases, pubmed-meshheading:17558399-Animals, pubmed-meshheading:17558399-Central Nervous System, pubmed-meshheading:17558399-Cerebral Cortex, pubmed-meshheading:17558399-Down-Regulation, pubmed-meshheading:17558399-Female, pubmed-meshheading:17558399-Fluorescent Antibody Technique, pubmed-meshheading:17558399-GPI-Linked Proteins, pubmed-meshheading:17558399-Immunoblotting, pubmed-meshheading:17558399-Immunoprecipitation, pubmed-meshheading:17558399-Ligands, pubmed-meshheading:17558399-Luciferases, pubmed-meshheading:17558399-Membrane Glycoproteins, pubmed-meshheading:17558399-Membrane Proteins, pubmed-meshheading:17558399-Mice, pubmed-meshheading:17558399-Mice, Inbred C57BL, pubmed-meshheading:17558399-Mice, Knockout, pubmed-meshheading:17558399-Neurons, pubmed-meshheading:17558399-Phenotype, pubmed-meshheading:17558399-Plasmids, pubmed-meshheading:17558399-Pregnancy, pubmed-meshheading:17558399-RNA Interference, pubmed-meshheading:17558399-Receptors, Notch, pubmed-meshheading:17558399-Recombinant Proteins, pubmed-meshheading:17558399-Retroviridae, pubmed-meshheading:17558399-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17558399-Signal Transduction
pubmed:year
2007
pubmed:articleTitle
RECK modulates Notch signaling during cortical neurogenesis by regulating ADAM10 activity.
pubmed:affiliation
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't