Neuralized-2 regulates a Notch ligand in cooperation with mind bomb-1

Ran Song, Bon Kyoung Koo, Ki Jun Yoon, Mi Jeong Yoon, Kyeong Won Yoo, Hyun Taek Kim, Hyeon Jeong Oh, Yoon Young Kim, Jin Kwan Han, Cheol Hee Kim, Young Yun Kong

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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 neurogenesis and somitogenesis. Thus, we speculated that other vertebrate neur homolog(s) might compensate for loss of the neur gene. Here, we report the paralog of mouse Neur1, named Neuralized-2 (Neur2), which is a ubiquitin-protein isopeptide ligase (E3) 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 those of neur1 in embryos, suggesting potential functional redundancy. Interestingly, two distinct classes of E3 ligases, Mind bomb-1 (Mib1) and Neur2, have cooperative but distinct roles in Delta endocytosis to Hrs-positive vesicles, i.e. 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 ligases work together in the endocytic pathways for Notch signaling.

Original languageEnglish (US)
Pages (from-to)36391-36400
Number of pages10
JournalJournal of Biological Chemistry
Issue number47
StatePublished - Nov 24 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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