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Notch Signaling during Oogenesis in Drosophila melanogaster.

Xu J, Gridley T - Genet Res Int (2012)

Bottom Line: The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism that is required for embryonic development, cell fate specification, and stem cell maintenance.Discovered and studied initially in Drosophila melanogaster, the Notch pathway is conserved and functionally active throughout the animal kingdom.In this paper, we summarize the biochemical mechanisms of Notch signaling and describe its role in regulating one particular developmental pathway, oogenesis in Drosophila.

View Article: PubMed Central - PubMed

Affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.

ABSTRACT
The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism that is required for embryonic development, cell fate specification, and stem cell maintenance. Discovered and studied initially in Drosophila melanogaster, the Notch pathway is conserved and functionally active throughout the animal kingdom. In this paper, we summarize the biochemical mechanisms of Notch signaling and describe its role in regulating one particular developmental pathway, oogenesis in Drosophila.

No MeSH data available.


Core components of the canonical Notch signaling pathway in Drosophila. The two Notch ligands encoded by the Serrate (Ser) and Delta (Dl) genes (upper cell) interact with an adjacent cell expressing the Notch receptor. The Notch receptor is proteolytically cleaved by a Furin protease in the Golgi and exists at the cell surface as a proteolytically cleaved heterodimer consisting of a large ectodomain and a membrane-tethered intracellular domain. The receptor/ligand interaction induces additional proteolytic cleavages by ADAM-family metalloproteases and the gamma-secretase complex in the membrane-tethered intracellular domain. The final cleavage, catalyzed by gamma-secretase, frees the Notch intracellular domain (NICD) from the cell membrane. NICD translocates to the nucleus, where it forms a complex with the Supressor of Hairless (Su(H)) protein, displacing a histone deacetylase (HDAc)/corepressor (CoR) complex from the Su(H) protein. Components of an activation complex such as the Mastermind (MAM) protein and histone acetyltransferases (HAc) are recruited to the NICD/Su(H) complex, leading to the transcriptional activation of Notch target genes.
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fig1: Core components of the canonical Notch signaling pathway in Drosophila. The two Notch ligands encoded by the Serrate (Ser) and Delta (Dl) genes (upper cell) interact with an adjacent cell expressing the Notch receptor. The Notch receptor is proteolytically cleaved by a Furin protease in the Golgi and exists at the cell surface as a proteolytically cleaved heterodimer consisting of a large ectodomain and a membrane-tethered intracellular domain. The receptor/ligand interaction induces additional proteolytic cleavages by ADAM-family metalloproteases and the gamma-secretase complex in the membrane-tethered intracellular domain. The final cleavage, catalyzed by gamma-secretase, frees the Notch intracellular domain (NICD) from the cell membrane. NICD translocates to the nucleus, where it forms a complex with the Supressor of Hairless (Su(H)) protein, displacing a histone deacetylase (HDAc)/corepressor (CoR) complex from the Su(H) protein. Components of an activation complex such as the Mastermind (MAM) protein and histone acetyltransferases (HAc) are recruited to the NICD/Su(H) complex, leading to the transcriptional activation of Notch target genes.

Mentions: The core mechanism of canonical Notch signaling is the release of NICD as a transcriptional regulator from the membrane (Figure 1). This process is activated by ligand-receptor interactions, and is controlled at many different levels (reviewed in [6, 21]). Activation of the canonical Notch signaling pathway is mediated by regulated sequential proteolysis. In mammals, the Notch protein is glycosylated by POFUT1 (protein O-fucosyltransferase 1) to produce a functional receptor. After proteolytic cleavage by PC5/6/FURIN (paired basic amino acid cleaving enzyme) at site S1, Notch receptors are targeted to the cell surface as a heterodimer. The O-fucose is extended by the glycosyltransferase activity of FRINGE proteins (O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, including lunatic, manic, and radical fringe in mammals), which regulate the ability of specific ligands to activate Notch receptors. The interaction with ligands leads to cleavage of Notch receptors by ADAM (a disintegrin and metallopeptidase domain) metalloproteases (ADAM10/Kuzbanian and ADAM17/TACE) at site S2, which is located about twelve amino acids before the transmembrane domain. In the absence of ligand, the S2 cleavage site is in a β-strand, deeply buried within the NRR [47]. After ligand binding, the Notch ectodomain is transendocytosed by ligand-presenting/signal-sending cells while the NICD is localized in signal-receiving cells [48]. Transendocytosis generates sufficient force to promote a conformational change that exposes S2 site for cleavage, which results in the generation of membrane bound intracellular Notch peptides (NEXT, for Notch extracellular truncation) [49, 50].


Notch Signaling during Oogenesis in Drosophila melanogaster.

Xu J, Gridley T - Genet Res Int (2012)

Core components of the canonical Notch signaling pathway in Drosophila. The two Notch ligands encoded by the Serrate (Ser) and Delta (Dl) genes (upper cell) interact with an adjacent cell expressing the Notch receptor. The Notch receptor is proteolytically cleaved by a Furin protease in the Golgi and exists at the cell surface as a proteolytically cleaved heterodimer consisting of a large ectodomain and a membrane-tethered intracellular domain. The receptor/ligand interaction induces additional proteolytic cleavages by ADAM-family metalloproteases and the gamma-secretase complex in the membrane-tethered intracellular domain. The final cleavage, catalyzed by gamma-secretase, frees the Notch intracellular domain (NICD) from the cell membrane. NICD translocates to the nucleus, where it forms a complex with the Supressor of Hairless (Su(H)) protein, displacing a histone deacetylase (HDAc)/corepressor (CoR) complex from the Su(H) protein. Components of an activation complex such as the Mastermind (MAM) protein and histone acetyltransferases (HAc) are recruited to the NICD/Su(H) complex, leading to the transcriptional activation of Notch target genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig1: Core components of the canonical Notch signaling pathway in Drosophila. The two Notch ligands encoded by the Serrate (Ser) and Delta (Dl) genes (upper cell) interact with an adjacent cell expressing the Notch receptor. The Notch receptor is proteolytically cleaved by a Furin protease in the Golgi and exists at the cell surface as a proteolytically cleaved heterodimer consisting of a large ectodomain and a membrane-tethered intracellular domain. The receptor/ligand interaction induces additional proteolytic cleavages by ADAM-family metalloproteases and the gamma-secretase complex in the membrane-tethered intracellular domain. The final cleavage, catalyzed by gamma-secretase, frees the Notch intracellular domain (NICD) from the cell membrane. NICD translocates to the nucleus, where it forms a complex with the Supressor of Hairless (Su(H)) protein, displacing a histone deacetylase (HDAc)/corepressor (CoR) complex from the Su(H) protein. Components of an activation complex such as the Mastermind (MAM) protein and histone acetyltransferases (HAc) are recruited to the NICD/Su(H) complex, leading to the transcriptional activation of Notch target genes.
Mentions: The core mechanism of canonical Notch signaling is the release of NICD as a transcriptional regulator from the membrane (Figure 1). This process is activated by ligand-receptor interactions, and is controlled at many different levels (reviewed in [6, 21]). Activation of the canonical Notch signaling pathway is mediated by regulated sequential proteolysis. In mammals, the Notch protein is glycosylated by POFUT1 (protein O-fucosyltransferase 1) to produce a functional receptor. After proteolytic cleavage by PC5/6/FURIN (paired basic amino acid cleaving enzyme) at site S1, Notch receptors are targeted to the cell surface as a heterodimer. The O-fucose is extended by the glycosyltransferase activity of FRINGE proteins (O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, including lunatic, manic, and radical fringe in mammals), which regulate the ability of specific ligands to activate Notch receptors. The interaction with ligands leads to cleavage of Notch receptors by ADAM (a disintegrin and metallopeptidase domain) metalloproteases (ADAM10/Kuzbanian and ADAM17/TACE) at site S2, which is located about twelve amino acids before the transmembrane domain. In the absence of ligand, the S2 cleavage site is in a β-strand, deeply buried within the NRR [47]. After ligand binding, the Notch ectodomain is transendocytosed by ligand-presenting/signal-sending cells while the NICD is localized in signal-receiving cells [48]. Transendocytosis generates sufficient force to promote a conformational change that exposes S2 site for cleavage, which results in the generation of membrane bound intracellular Notch peptides (NEXT, for Notch extracellular truncation) [49, 50].

Bottom Line: The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism that is required for embryonic development, cell fate specification, and stem cell maintenance.Discovered and studied initially in Drosophila melanogaster, the Notch pathway is conserved and functionally active throughout the animal kingdom.In this paper, we summarize the biochemical mechanisms of Notch signaling and describe its role in regulating one particular developmental pathway, oogenesis in Drosophila.

View Article: PubMed Central - PubMed

Affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.

ABSTRACT
The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism that is required for embryonic development, cell fate specification, and stem cell maintenance. Discovered and studied initially in Drosophila melanogaster, the Notch pathway is conserved and functionally active throughout the animal kingdom. In this paper, we summarize the biochemical mechanisms of Notch signaling and describe its role in regulating one particular developmental pathway, oogenesis in Drosophila.

No MeSH data available.