Mind bomb 1 is essential for generating functional Notch ligands to activate Notch
Author:
Koo Bon-Kyoung1, Lim Hyoung-Soo1, Song Ran1, Yoon Mi-Jeong1, Yoon Ki-Jun1, Moon Jin-Sook1, Kim Young-Woong1, Kwon Min-chul1, Yoo Kyeong-Won2, Kong Myung-Phil1, Lee Jinie1, Chitnis Ajay B.3, Kim Cheol-Hee2, Kong Young-Yun1
Affiliation:
1. Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, South Korea 2. Department of Biology, Chungnam National University, Taejeon 305-764, South Korea 3. Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892, USA
Abstract
The Delta-Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for cell fate specification. Mind bomb 1 (Mib1) has been identified as a ubiquitin ligase that promotes the endocytosis of Delta. We now report that mice lacking Mib1 die prior to embryonic day 11.5, with pan-Notch defects in somitogenesis, neurogenesis,vasculogenesis and cardiogenesis. The Mib1–/–embryos exhibit reduced expression of Notch target genes Hes5, Hey1, Hey2 and Heyl, with the loss of N1icd generation. Interestingly, in the Mib1–/–mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types, indicating that Mib1 is essential for the endocytosis of Notch ligand. In accordance with the pan-Notch defects in Mib1–/– embryos, Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2,as well as Dll1, Dll3 and Dll4. Our results show that Mib1 is an essential regulator, but not a potentiator, for generating functional Notch ligands to activate Notch signaling.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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