Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal

Hori, Kenta; Sen, Anindya; Kirchhausen, Tomas; Artavanis‐Tsakonas, Spyros

doi:10.1083/jcb.201104146

Cited by 107 publications

(147 citation statements)

References 59 publications

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“…shrub, Dx, and Kurtz regulate Notch trafficking and consequently its degradation in the late endosomal compartment (Hori et al 2011). Hence two different roles in Notch regulation have been ascribed to Dx, depending on the tissue type and developmental context.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Notch Signaling by an Evolutionary Conserved DEAD Box RNA Helicase, Maheshvara in Drosophila melanogaster

Surabhi¹,

Tripathi²,

Maurya³

et al. 2015

Genetics

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Notch signaling is an evolutionary conserved process that influences cell fate determination, cell proliferation, and cell death in a context-dependent manner. Notch signaling is fine-tuned at multiple levels and misregulation of Notch has been implicated in a variety of human diseases. We have characterized maheshvara (mahe), a novel gene in Drosophila melanogaster that encodes a putative DEAD box protein that is highly conserved across taxa and belongs to the largest group of RNA helicase. A dynamic pattern of mahe expression along with the maternal accumulation of its transcripts is seen during early stages of embryogenesis. In addition, a strong expression is also seen in the developing nervous system. Ectopic expression of mahe in a wide range of tissues during development results in a variety of defects, many of which resemble a typical Notch loss-of-function phenotype. We illustrate that ectopic expression of mahe in the wing imaginal discs leads to loss of Notch targets, Cut and Wingless. Interestingly, Notch protein levels are also lowered, whereas no obvious change is seen in the levels of Notch transcripts. In addition, mahe overexpression can significantly rescue ectopic Notch-mediated proliferation of eye tissue. Further, we illustrate that mahe genetically interacts with Notch and its cytoplasmic regulator deltex in trans-heterozygous combination. Coexpression of Deltex and Mahe at the dorso-ventral boundary results in a wing-nicking phenotype and a more pronounced loss of Notch target Cut. Taken together we report identification of a novel evolutionary conserved RNA helicase mahe, which plays a vital role in regulation of Notch signaling. KEYWORDS Drosophila; DEAD box helicase; Notch signaling; RNA-binding protein; RNA helicase N OTCH signaling is an evolutionary conserved process that mediates cell-cell communication, which ultimately regulates cell fate (Artavanis-Tsakonas et al. 1999). Notch signaling is critical for many developmental processes and aberrant notch signaling has been related to many human diseases including cancer (Gridley 2003). Notch encodes a trans-membrane receptor that comprises an extracellular domain (NECD) and an intracellular domain (NICD). Notch is expressed at the cell surface as a heterodimeric receptor that is a result of furin-dependent cleavage (S1) occurring in the trans-Golgi network. At the cell surface it physically interacts with the ligands that are expressed in the apposing cells. This interaction with the ligand facilitates a series of proteolytic cleavages, ultimately resulting in the release of NICD. Released NICD translocates into the nucleus, where it interacts with a DNA binding protein CSL (mammalian CBF1/Drosophila Suppressor of Hairless/C. elegans Lag-1) and activates downstream gene expression, by relieving the repressor complex that silences Notch target genes (ArtavanisTsakonas et al. 1983;Logeat et al. 1998;Struhl and Greenwald 1999;Brou et al. 2000;Kopan 2002;Lieber et al. 2002). Finetuning of Notch signaling is mediated by a vast num...

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Section: Discussionmentioning

confidence: 99%

Regulation of Notch Signaling by an Evolutionary Conserved DEAD Box RNA Helicase, Maheshvara in Drosophila melanogaster

Surabhi¹,

Tripathi²,

Maurya³

et al. 2015

Genetics

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show abstract

“…This factor interacts with components of the AP-2 complex and prevents endosome-to-plasma membrane recycling of Notch; in addition, Numb also promotes the lysosomal degradation of the receptor (McGill et al, 2009). In contrast, Deltex, an E3 ligase, has been shown to promote Notch signaling in a ligand-independent manner (Sakata et al, 2004;Wilkin et al, 2008;Hori et al, 2011Hori et al, , 2012Troost et al, 2012). Acting in concert with the homotypic fusion and protein sorting complex and Rab7, Deltex promotes the trafficking of Notch to late endosomes.…”

Section: Discussionmentioning

confidence: 99%

Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling

Li¹,

Koo²,

Mao³

et al. 2015

J Exp Med

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“…This study reveals that endosomal trafficking exerts a necessary dampening effect on Notch signaling. In addition, recent work has indicated that Notch activation at the endosome, occurs independently of the ligand (Childress et al, 2006;Hori et al, 2011). This might explain why, in neurons, Notch processing is positively regulated by the endosomal trafficking molecule, Arc, regardless of ligand availability (Alberi et al, 2011) (Fig.…”

Section: Endocytic Internalization Of Notchmentioning

confidence: 99%

Notch signaling in the brain: In good and bad times

Albèri

Hoey

Brai

et al. 2013

Ageing Research Reviews

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Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal

Abstract: The ESCRT-III complex component Shrub plays a pivotal rate-limiting step in late endosomal ligand-independent Notch activation.

Cited by 107 publications

References 59 publications

Regulation of Notch Signaling by an Evolutionary Conserved DEAD Box RNA Helicase, Maheshvara in Drosophila melanogaster

Regulation of Notch Signaling by an Evolutionary Conserved DEAD Box RNA Helicase, Maheshvara in Drosophila melanogaster

Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling

Notch signaling in the brain: In good and bad times

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