Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi

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Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi.

Protein O-glucosylation is a conserved post-translational modification that occurs on epidermal growth factor-like (EGF) repeats harboring the C(1)-X-S-X-P-C(2) consensus sequence. The Drosophila protein O-glucosyltransferase (Poglut) Rumi regulates Notch signaling, but the contribution of protein O-glucosylation to mammalian Notch signaling and embryonic development is not known. Here, we show...

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Rumi functions as both a protein O-glucosyltransferase and a protein O-xylosyltransferase.

Mutations in rumi result in a temperature-sensitive loss of Notch signaling in Drosophila. Drosophila Rumi is a soluble, endoplasmic reticulum-retained protein with a CAP10 domain that functions as a protein O-glucosyltransferase. In human and mouse genomes, three potential Rumi homologues exist: one with a high degree of identity to Drosophila Rumi (52%), and two others with lower degrees of i...

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Dendritic patterning exerts a profound influence on neuronal connectivity. Recent studies indicate that mammalian Notch receptors are expressed by postmitotic neurons and that Notch signaling has a considerable influence on dendritic growth and branching. Investigations into the intracellular effectors of dendritic development have revealed that dendritic growth and branching are differentially...

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The Protein O-glucosyltransferase Rumi Modifies Eyes Shut to Promote Rhabdomere Separation in Drosophila

The protein O-glucosyltransferase Rumi/POGLUT1 regulates Drosophila Notch signaling by adding O-glucose residues to the Notch extracellular domain. Rumi has other predicted targets including Crumbs (Crb) and Eyes shut (Eys), both of which are involved in photoreceptor development. However, whether Rumi is required for the function of Crb and Eys remains unknown. Here we report that in the absen...

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Notch and its ligands are modified by a protein O-fucosyltransferase (OFUT1) that attaches fucose to a Serine or Threonine within EGF domains. By using RNAi to decrease Ofut1 expression in Drosophila, we demonstrate that O-linked fucose is positively required for Notch signaling, including both Fringe-dependent and Fringe-independent processes. The requirement for Ofut1 is cell autonomous, in t...

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ژورنال

عنوان ژورنال: Developmental Biology

سال: 2011

ISSN: 0012-1606

DOI: 10.1016/j.ydbio.2011.05.088