Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta

Motoyuki Itoh; Cheol-Hee Kim; Gregory Palardy; Takaya Oda; Yun-Jin Jiang; Donovan Maust; Sang-Yeob Yeo; Kevin Lorick; Gavin J Wright; Linda Ariza-McNaughton; Allan M Weissman; Julian Lewis; Settara C Chandrasekharappa; Ajay B Chitnis

doi:10.1016/s1534-5807(02)00409-4

Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta

Dev Cell. 2003 Jan;4(1):67-82. doi: 10.1016/s1534-5807(02)00409-4.

Authors

Motoyuki Itoh¹, Cheol-Hee Kim, Gregory Palardy, Takaya Oda, Yun-Jin Jiang, Donovan Maust, Sang-Yeob Yeo, Kevin Lorick, Gavin J Wright, Linda Ariza-McNaughton, Allan M Weissman, Julian Lewis, Settara C Chandrasekharappa, Ajay B Chitnis

Affiliation

¹ Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892, USA.

PMID: 12530964
DOI: 10.1016/s1534-5807(02)00409-4

Abstract

Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Cell Differentiation
Endocytosis
Gene Expression Regulation
In Situ Hybridization
Intracellular Signaling Peptides and Proteins
Ligases / chemistry
Ligases / genetics
Ligases / metabolism*
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Molecular Sequence Data
Neurons / cytology
Neurons / metabolism*
Phenotype
Protein Structure, Tertiary
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Notch
Signal Transduction*
Spinal Cord / embryology
Spinal Cord / metabolism
Ubiquitin / metabolism*
Ubiquitin-Protein Ligases*
Zebrafish / embryology
Zebrafish / genetics
Zebrafish / metabolism*
Zebrafish Proteins / chemistry
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism*

Substances

Intracellular Signaling Peptides and Proteins
Membrane Proteins
RNA, Messenger
Receptors, Notch
Ubiquitin
Zebrafish Proteins
delta protein
Ubiquitin-Protein Ligases
mib1 protein, zebrafish
Ligases

Associated data

GENBANK/AF149907
GENBANK/AF149908
GENBANK/AF537301