Neuralized-2 regulates a Notch ligand in cooperation with Mind bomb-1.
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.
Song
Ran
R
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, South Korea.
Koo
Bon-Kyoung
BK
Yoon
Ki-Jun
KJ
Yoon
Mi-Jeong
MJ
Yoo
Kyeong-Won
KW
Kim
Hyun-Taek
HT
Oh
Hyeon-Jeong
HJ
Kim
Yoon-Young
YY
Han
Jin-Kwan
JK
Kim
Cheol-Hee
CH
Kong
Young-Yun
YY
D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism* / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D008024:Ligands; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; C438900:Neurl protein, mouse; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C470629:MIB1 protein, mouse; C502570:Mib1 protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish; C071006:neur protein, Drosophila