Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1.
Elife
; 62017 08 04.
Article
em En
| MEDLINE
| ID: mdl-28826503
ABSTRACT
Mutations in the human N-glycanase 1 (NGLY1) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N-glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N-glycanase enzyme.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Morfogenéticas Ósseas
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Proteínas de Drosophila
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Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase
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Drosophila
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos