Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling.
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.
Acar
Melih
M
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jafar-Nejad
Hamed
H
Takeuchi
Hideyuki
H
Rajan
Akhila
A
Ibrani
Dafina
D
Rana
Nadia A
NA
Pan
Hongling
H
Haltiwanger
Robert S
RS
Bellen
Hugo J
HJ
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes; D016384:Consensus Sequence; D004330:Drosophila / Q000737:chemistry / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000172:deficiency; D004625:Embryo, Nonmammalian; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D017344:Genes, Insect; D005947:Glucose / Q000378:metabolism; D005964:Glucosyltransferases / Q000172:deficiency; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006720:Homozygote; D007150:Immunohistochemistry; D008954:Models, Biological; D009154:Mutation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility; D018411:Spodoptera / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D019076:Transgenes
D029721:Drosophila Proteins; D051880:Receptors, Notch; D012694:Serine; D016695:Glycosyltransferases; D005964:Glucosyltransferases; C527374:Rumi protein, Drosophila; D005947:Glucose