PUBLICATION

Nicalin and its binding partner Nomo are novel Nodal signaling antagonists

Authors
Haffner, C., Frauli, M., Topp, S., Irmler, M., Hofmann, K., Regula, J.T., Bally-Cuif, L., and Haass, C.
ID
ZDB-PUB-040719-9
Date
2004
Source
The EMBO journal   23(15): 3041-3050 (Journal)
Registered Authors
Bally-Cuif, Laure, Haass, Christian, Topp, Stefanie
Keywords
Lefty, mesoderm, Nicastrin, Nodal, pM5
MeSH Terms
  • Molecular Weight
  • Protein Binding
  • Prosencephalon/embryology
  • Prosencephalon/metabolism
  • Signal Transduction*
  • Membrane Glycoproteins/genetics
  • Membrane Glycoproteins/metabolism*
  • Somites/metabolism
  • Phylogeny
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Transforming Growth Factor beta/metabolism*
  • Gene Expression Regulation, Developmental
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Multiprotein Complexes/chemistry
  • Multiprotein Complexes/metabolism
  • Nodal Protein
  • Animals
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Cell Line
  • Body Patterning
  • Amyloid Precursor Protein Secretases
  • Intracellular Signaling Peptides and Proteins
  • Humans
PubMed
15257293 Full text @ EMBO J.
Abstract
Nodals are signaling factors of the transforming growth factor-beta (TGFbeta) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the establishment of the embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), as novel antagonists of Nodal signaling. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo. Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an increase in anterior axial mesendoderm and the development of an enlarged hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish.
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