ArticleMolecular biology of the cell2007
The NHR1 domain of Neuralized binds Delta and mediates Delta trafficking and Notch signaling.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Human Neuralized is a novel tumour suppressor targeting Wnt/β-catenin signalling in colon cancer.EMBO reports · 2023Article
- Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A.Scientific reports · 2019Article
- Article
- Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms.The Journal of cell biology · 2017Article
- The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway.PLoS genetics · 2015Article
- Neural precursor-specific expression of multiple Drosophila genes is driven by dual enhancer modules with overlapping function.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Tools and methods for studying Notch signaling in Drosophila melanogaster.Methods (San Diego, Calif.) · 2014Article
- Functional analysis of the NHR2 domain indicates that oligomerization of Neuralized regulates ubiquitination and endocytosis of Delta during Notch signaling.Molecular and cellular biology · 2012Article
- Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes.Molecular and cellular biology · 2012Article
- Regulation of developmental intercellular signalling by intracellular trafficking.The EMBO journal · 2011Review
- Notch ligand ubiquitylation: what is it good for?Developmental cell · 2011Review
- Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma.Neuro-oncology · 2010Article
- Neuralized promotes basal to apical transcytosis of delta in epithelial cells.Molecular biology of the cell · 2010Article
- Endocytosis and intracellular trafficking of Notch and its ligands.Current topics in developmental biology · 2010Review
- Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes.BMC evolutionary biology · 2009Article
- Numb regulates post-endocytic trafficking and degradation of Notch1.The Journal of biological chemistry · 2009Article
- Article
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2 authors.
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Abstract
Notch signaling, which is crucial to metazoan development, requires endocytosis of Notch ligands, such as Delta and Serrate. Neuralized is a plasma membrane-associated ubiquitin ligase that is required for neural development and Delta internalization. Neuralized is comprised of three domains that include a C-terminal RING domain and two neuralized homology repeat (NHR) domains. All three domains are conserved between organisms, suggesting that these regions of Neuralized are functionally important. Although the Neuralized RING domain has been shown to be required for Delta ubiquitination, the function of the NHR domains remains elusive. Here we show that neuralized, a well-characterized neurogenic allele, exhibits a mutation in a conserved residue of the NHR1 domain that results in mislocalization of Neuralized and defects in Delta binding and internalization. Furthermore, we describe a novel isoform of Neuralized and show that it is recruited to the plasma membrane by Delta and that this is mediated by the NHR1 domain. Finally, we show that the NHR1 domain of Neuralized is both necessary and sufficient to bind Delta. Altogether, our data demonstrate that NHR domains can function in facilitating protein-protein interactions and in the case of Neuralized, mediate binding to its ubiquitination target, Delta.
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