The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability.
Biol Res
; 44(1): 25-34, 2011.
Article
em En
| MEDLINE
| ID: mdl-21720678
The Notch signaling pathway plays an important role in development and physiology. In Drosophila, Notch is activated by its Delta or Serrate ligands, depending in part on the sugar modifications present in its extracellular domain. O-fucosyltransferase-1 (OFUT1) performs the first glycosylation step in this process, O-fucosylating various EGF repeats at the Notch extracellular domain. Besides its O-fucosyltransferase activity, OFUT1 also behaves as a chaperone during Notch synthesis and is able to down regulate Notch by enhancing its endocytosis and degradation. We have reevaluated the roles that O-fucosylation and the synthesis of GDP-fucose play in the regulation of Notch protein stability. Using mutants and the UAS/Gal4 system, we modified in developing tissues the amount of GDP-mannose-deshydratase (GMD), the first enzyme in the synthesis of GDP-fucose. Our results show that GMD activity, and likely the levels of GDP-fucose and O-fucosylation, are essential to stabilize the Notch protein. Notch degradation observed under low GMD expression is absolutely dependent on OFUT1 and this is also observed in Notch Abruptex mutants, which have mutations in some potential O-fucosylated EGF domains. We propose that the GDP-fucose/OFUT1 balance determines the ability of OFUT1 to endocytose and degrade Notch in a manner that is independent of the residues affected by Abruptex mutations in Notch EGF domains.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asas de Animais
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Proteínas de Drosophila
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Drosophila melanogaster
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Receptores Notch
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Fucosiltransferases
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Guanosina Difosfato Fucose
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Guanosina Difosfato Manose
Limite:
Animals
Idioma:
En
Revista:
Biol Res
Assunto da revista:
BIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Espanha
País de publicação:
Reino Unido