title: The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity.
abstract: Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Abbruzzese
authors.affiliation: Section Developmental Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg D-69120, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Gorny
authors.affiliation: Section Developmental Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg D-69120, Germany.
authors.forename: Lilian T
authors.initials: LT
authors.lastname: Kaufmann
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Hélène
authors.initials: H
authors.lastname: Cousin
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Iivari
authors.initials: I
authors.lastname: Kleino
authors.affiliation: Section Developmental Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg D-69120, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Steinbeisser
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA alfandar@vasci.umass.edu.
authors.forename: Dominique
authors.initials: D
authors.lastname: Alfandari
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
chemical_list: D051157:Frizzled Receptors; D008565:Membrane Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051722:ADAM Proteins; C104937:ADAM33 protein, Xenopus
keywords: ADAM; Development; Neural crest; Wnt; Xenopus laevis