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PMID:18243100

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Citation

Acar, M, Jafar-Nejad, H, Takeuchi, H, Rajan, A, Ibrani, D, Rana, NA, Pan, H, Haltiwanger, RS and Bellen, HJ (2008) Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 132:247-58

Abstract

Notch signaling is broadly used to regulate cell-fate decisions. We have identified a gene, rumi, with a temperature-sensitive Notch phenotype. At 28 degrees C-30 degrees C, rumi clones exhibit a full-blown loss of Notch signaling in all tissues tested. However, at 18 degrees C only a mild Notch phenotype is evident. In vivo analyses reveal that the target of Rumi is the extracellular domain of Notch. Notch accumulates intracellularly and at the cell membrane of rumi cells but fails to be properly cleaved, despite normal binding to Delta. Rumi is an endoplasmic reticulum-retained protein with a highly conserved CAP10 domain. Our studies show that Rumi is a protein O-glucosyltransferase, capable of adding glucose to serine residues in Notch EGF repeats with the consensus C1-X-S-X-P-C2 sequence. These data indicate that by O-glucosylating Notch in the ER, Rumi regulates its folding and/or trafficking and allows signaling at the cell membrane.

Links

PubMed PMC2275919 Online version:10.1016/j.cell.2007.12.016

Keywords

Alleles; Amino Acid Sequence; Animals; Chromosome Mapping; Chromosomes; Consensus Sequence; Drosophila/chemistry; Drosophila/embryology; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins/deficiency; Embryo, Nonmammalian; Endoplasmic Reticulum/metabolism; Gene Expression Regulation; Genes, Insect; Glucose/metabolism; Glucosyltransferases/deficiency; Glycosylation; Glycosyltransferases/chemistry; Glycosyltransferases/genetics; Glycosyltransferases/metabolism; Glycosyltransferases/physiology; Homozygote; Immunohistochemistry; Models, Biological; Mutation; Protein Folding; Protein Structure, Tertiary; RNA Interference; Receptors, Notch/genetics; Receptors, Notch/metabolism; Serine/metabolism; Signal Transduction; Solubility; Spodoptera/cytology; Spodoptera/genetics; Spodoptera/metabolism; Temperature; Transgenes

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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