The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability

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...

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Autores principales:	Glavic,Alvaro, López-Varea,Ana, de Celis,José F
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2011
Materias:	Notch GMD O-fucosyltranserase Drosophila
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000100004
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spelling	oai:scielo:S0716-976020110001000042011-09-01The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stabilityGlavic,AlvaroLópez-Varea,Anade Celis,José F Notch GMD O-fucosyltranserase Drosophila 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.44 n.1 20112011-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000100004en10.4067/S0716-97602011000100004
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Notch GMD O-fucosyltranserase Drosophila
spellingShingle	Notch GMD O-fucosyltranserase Drosophila Glavic,Alvaro López-Varea,Ana de Celis,José F The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability
description	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.
author	Glavic,Alvaro López-Varea,Ana de Celis,José F
author_facet	Glavic,Alvaro López-Varea,Ana de Celis,José F
author_sort	Glavic,Alvaro
title	The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability
title_short	The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability
title_full	The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability
title_fullStr	The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability
title_full_unstemmed	The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability
title_sort	balance between gmd and ofut1 regulates notch signaling pathway activity by modulating notch stability
publisher	Sociedad de Biología de Chile
publishDate	2011
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000100004
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The balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability

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