ZFIN ID: ZDB-PUB-061021-1
Neuralized-2 regulates notch ligand in cooperation with mind bomb-1
Song, R., Koo, B.K., Yoon, K.J., Yoon, M.J., Yoo, K.W., Kim, H.T., Oh, H.J., Kim, Y.Y., Han, J.K., Kim, C.H., and Kong, Y.Y.
Date: 2006
Source: The Journal of biological chemistry   281(47): 36391-36400 (Journal)
Registered Authors: Kim, Cheol-Hee, Kim, Hyun-Taek, Yoo, Kyeong-Won
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins/metabolism*
  • Drosophila Proteins/physiology*
  • Drosophila melanogaster
  • Humans
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Nerve Tissue Proteins/metabolism
  • Nerve Tissue Proteins/physiology*
  • Receptors, Notch/metabolism*
  • Sequence Homology, Amino Acid
  • Ubiquitin-Protein Ligases/metabolism*
  • Ubiquitin-Protein Ligases/physiology*
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 17003037 Full text @ J. Biol. Chem.
Mutations in Drosophila neuralized (Dneur) result in a variety of developmental defects that closely resemble those of Notch mutants and other Notch pathway mutants. However, mice with disrupted neur1 do not show any aberrant cell fate specifications in the neurogenesis and somitogenesis. Thus, we speculate that other vertebrate neur homologue(s) might compensate for loss of the neur gene. Here, we report the paralogue of mouse Neur1, named Neuralized-2 (Neur2), which is an E3 ubiquitin ligase that interacts with and ubiquitinates Delta. Both murine Neur1 and Neur2 have similar degrees of homology to DNeur and neur2 is expressed in patterns similar to that of neur1 in the embryos, suggesting potential functional redundancy. Interestingly, two distinct classes of E3 ubiquitin ligases, Mind bomb-1 (Mib1) and Neur2, have cooperative but distinct roles in Delta endocytosis to Hrs-positive vesicles, that is, Mib1 functions in the initial step of Delta endocytosis and Neur2 is required for targeting endocytosed Delta to Hrs-positive vesicles. Thus, our study provides a new insight into how distinct E3 ubiquitin ligases work together in the endocytic pathways for Notch signaling.