2005
DOI: 10.1038/nn1492
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DNER acts as a neuron-specific Notch ligand during Bergmann glial development

Abstract: Differentiation of CNS glia is regulated by Notch signaling through neuron-glia interaction. Here, we identified Delta/Notch-like EGF-related receptor (DNER), a neuron-specific transmembrane protein, as a previously unknown ligand of Notch during cellular morphogenesis of Bergmann glia in the mouse cerebellum. DNER binds to Notch1 at cell-cell contacts and activates Notch signaling in vitro. In the developing cerebellum, DNER is highly expressed in Purkinje cell dendrites, which are tightly associated with rad… Show more

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Cited by 204 publications
(215 citation statements)
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“…1 and 2, although larger portions of mN1 (e.g. EGF [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] were also analyzed to confirm that utilization of glycosylation sites was not affected by the size of the fragment being analyzed. Modified peptides were identified by neutral loss of the O-glucose saccharides upon low energy CID fragmentation.…”
Section: Mouse Notch1 Is Extensively Modified With O-glucose Inmentioning
confidence: 99%
See 1 more Smart Citation
“…1 and 2, although larger portions of mN1 (e.g. EGF [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] were also analyzed to confirm that utilization of glycosylation sites was not affected by the size of the fragment being analyzed. Modified peptides were identified by neutral loss of the O-glucose saccharides upon low energy CID fragmentation.…”
Section: Mouse Notch1 Is Extensively Modified With O-glucose Inmentioning
confidence: 99%
“…Upon ligand binding, Notch undergoes presenilin-1-dependent proteolysis, releasing a soluble Notch intracellular domain, which enters the cell nucleus to interact directly with the transcription factors from the CSL family and regulate Notch target genes (2). There are four members of the Notch family in vertebrates (Notch1 to Notch4) interacting with several classes of Notch ligands: ligands of the DSL family (Delta-like 1, 3, and 4 and Jagged 1 and 2) (1) and newly characterized ligands without the DSL domain, such as DNER and MAGP-1 and -2 (11)(12)(13).…”
mentioning
confidence: 99%
“…Studies in vivo provide evidence that the expression of glutamate transporters in the mammalian CNS is regulated by neuron-glial communication during development and also at mature stages. In the developing rodent cerebellum, for example, neuron-glial signaling through Notch and its ligand DNER regulates the maturation of Bergmann glia and promotes GLAST expression in these specialized astrocytes (Eiraku et al, 2005). Interestingly, the Fng ortholog Lunatic Fringe is expressed in Bergmann glia (Gong et al, 2003), but its involvement in neuron-glial interactions there remains unknown.…”
Section: Differentiation Of Functionally Distinct Glial Cell Subtypesmentioning
confidence: 99%
“…DNER is a single-pass transmembrane protein containing ten epidermal growth factor-like repeats in the extracellular domain, similar to those of delta-like, Jagged, and Notch proteins (Eiraku et al 2002, Nishizumi et al 2002. In the cerebellum, where the role of DNER has been particularly well examined, this molecule promotes morphological and functional maturation of glia through intercellular activation of Notch signaling (Eiraku et al 2005, Saito and Takeshima 2006, Tohgo et al 2006. DNER binds to Notch1 at cell-cell contacts and stimulates Notch intracellular domain cleavage and CSL-dependent transcription in C2C12 myoblasts (Eiraku et al 2005).…”
Section: Introductionmentioning
confidence: 99%
“…In the cerebellum, where the role of DNER has been particularly well examined, this molecule promotes morphological and functional maturation of glia through intercellular activation of Notch signaling (Eiraku et al 2005, Saito and Takeshima 2006, Tohgo et al 2006. DNER binds to Notch1 at cell-cell contacts and stimulates Notch intracellular domain cleavage and CSL-dependent transcription in C2C12 myoblasts (Eiraku et al 2005). In addition, DNER expressed in Purkinje neurons, induces Bergman glial process extension and maturation through gamma-secretase-and Deltex-dependent, CSLindependent (non-canonical) Notch signaling (Eiraku et al 2005).…”
Section: Introductionmentioning
confidence: 99%