The roles of receptor and ligand endocytosis in regulating Notch signaling

Borgne, Roland Le; Bardin, Allison J.; Schweisguth, François

doi:10.1242/dev.01789

Cited by 299 publications

(298 citation statements)

References 114 publications

(130 reference statements)

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“…In mammals, the Delta-like and Jagged ligands mature as a result of cleavages by tumor necrosis factor α-converting enzyme-like protease and γ-secretase, and could be released as extracellular soluble forms (38). Furthermore, Notch ligands may also be released extracellularly via secreted vesicles (39). Besides Delta and Jagged family members, CCN3 and MAGPs can function as the Notch ligand, causing dissociation of the Notch1 extracellular domain and activation of the receptor (9).…”

Section: Discussionmentioning

confidence: 99%

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Hosaka¹,

Saito

Sugita³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

164

165

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Here we examined the involvement of Notch signaling in the endochondral ossification process, which is crucial for osteoarthritis (OA) development. Intracellular domains of Notch1 and -2 were translocated into the nucleus of chondrocytes with their differentiation in mouse limb cartilage and in mouse and human OA articular cartilage. A tissue-specific inactivation of the Notch transcriptional effector recombination signal binding protein for Ig kappa J (RBPjκ) in chondroprogenitor cells of SRY-box containing gene 9 (Sox9) -Cre ;Rbpj fl/fl mouse embryos caused an impaired terminal stage of endochondral ossification in the limb cartilage. The RBPjκ inactivation in adult articular cartilage after normal skeletal growth using type II collagen ( Col2a1 )- Cre ERT ;Rbpj fl/fl mice by tamoxifen injection caused resistance to OA development in the knee joint. Notch intracellular domain with the effector RBPjκ stimulated endochondral ossification through induction of the target gene Hes1 in chondrocytes. Among the Notch ligands, Jagged1 was strongly induced during OA development. Finally, intraarticular injection of N -[ N -(3,5-diflurophenylacetate)- l -alanyl]-(S)-phenylglycine t-butyl ester (DAPT), a small compound Notch inhibitor, to the mouse knee joint prevented OA development. The RBPjκ-dependent Notch signaling in chondrocytes modulates the terminal stage of endochondral ossification and OA development, representing an extracellular therapeutic target of OA.

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Section: Discussionmentioning

confidence: 99%

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Hosaka¹,

Saito

Sugita³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

164

165

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“…It is often thought that signalling events have specific proteins associated with them and thus the notion of signal transduction pathways as a constellation of proteins dedicated to a signalling event. Recent genetic studies in Drosophila have revealed that an increasing number of proteins involved in intracellular traffic are required for the activity of Notch (reviewed in (Le Borgne et al 2005a)). For example, mutants producing defects on endocytosis, recycling, vesicular sorting and multivesicular body formation present defects on Notch signalling (Poodry 1990, Ramain et al 2001, Thompson et al 2005, Vaccari & Bilder 2005, Jaekel & Klein 2006.…”

Section: Notch Traffickingmentioning

confidence: 99%

“…There is some recent experimental evidence in favour of this model (Nichols et al 2007). Another possibility is that ligand endocytosis is required for ligand post-translational modifications which render the ligand competent for activating Notch signalling activity when recycled back to the plasma membrane (Wang & Struhl 2004, Le Borgne et al 2005a, Wilkin & Baron 2005). The latter model is supported by the fact that Delta lacking its intracellular domain is not able to elicit Notch signalling activity (Sun & Artavanis-Tsakonas 1996, Nichols et al 2007).…”

Section: Ligand Traffickingmentioning

confidence: 99%

Cell and molecular biology of Notch

Fiúza

Arias

2007

Journal of Endocrinology

319

291

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Notch signalling is a cell-cell communication process, which allows the establishment of patterns of gene expression and differentiation, regulates binary cell fate choice and the maintenance of stem cell populations. So far, the data published has elucidated the main players in the Notch signalling pathway. However, its regulatory mechanisms are exhibiting an increasing complexity which could account for the multitude of roles it has during development and in adult organisms. In this review, we will describe the multiple roles of Notch and how various factors can regulate Notch signalling.

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“…The discrepancies in our findings may be due to differences in which proliferation of VNC and central brain NBs are regulated. To test whether Notch might be hyperactivated in aurA mutants, we examined the membrane localization of Sanpodo (Spdo), which is required to activate Notch but is inhibited by Numb during GMC and SOP asymmetric divisions (O'Connor-Giles and Skeath 2003;Le Borgne et al 2005). In wild-type interphase larval NBs, Spdo displayed a weak cortical staining and in punctate structures throughout the cytoplasm (100%, n = 38; Fig.…”

Section: The Role Of Notch In Nb Proliferationmentioning

confidence: 99%

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

Wang¹,

Somers²,

Bashirullah³

et al. 2006

Genes Dev.

248

294

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The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides terminally to produce two differentiating neuronal/glial daughters. Here we show that Aurora-A (AurA) acts as a tumor suppressor by suppressing NB self-renewal and promoting neuronal differentiation. In aurA loss-of-function mutants, supernumerary NBs are produced at the expense of neurons. AurA suppresses tumor formation by asymmetrically localizing atypical protein kinase C (aPKC), an NB proliferation factor. Numb, which also acts as a tumor suppressor in larval brains, is a major downstream target of AurA and aPKC. Notch activity is up-regulated in aurA and numb larval brains, and Notch signaling is necessary and sufficient to promote NB self-renewal and suppress differentiation in larval brains. Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway that involved a series of negative genetic interactions. We have identified a novel mechanism for controlling the balance between self-renewal and neuronal differentiation during the asymmetric division of Drosophila larval NBs.[Keywords: Neuroblast; stem cells; asymmetric division; tumor suppressor; self-renewal] Supplemental material is available at http://www.genesdev.org.

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The roles of receptor and ligand endocytosis in regulating Notch signaling

Cited by 299 publications

References 114 publications

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Cell and molecular biology of Notch

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

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