EphrinB3 is an anti-apoptotic ligand that inhibits the dependence receptor functions of EphA4 receptors during adult neurogenesis

Furne, Céline; Ricard, Jacques; Cabrera, Jorge Rubén; Pays, Laurent; Bethea, John R.; Mehlen, Patrick; Liebl, Daniel J.

doi:10.1016/j.bbamcr.2008.09.009

Cited by 85 publications

(128 citation statements)

References 35 publications

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“…The main hypothesis with regard to the role of ligand binding is inhibition of the caspase cleavage. This hypothesis has been partly confirmed for some DRs, UNC5H2 (Tanikawa et al, 2003), TrkC (Tauszig-Delamasure et al, 2007), EphA4 (Furne et al, 2009) and MET (Tulasne et al, 2004;Foveau et al, 2007). For other receptors, the effect of ligand on caspase cleavage cannot be assessed because cleavage products have relatively short half-lives and are thus hardly detectable in vivo.…”

Section: Role Of Ligand Bindingmentioning

confidence: 93%

“…Activation of EphA7 by overexpressed ephrinA5 in the embryonic cortex resulted in neural progenitor apoptosis (Depaepe et al, 2005). On the other hand, lack of ephrinB3 is associated with apoptosis in the subventricular zone of adult mice (Ricard et al, 2006), suggesting that its receptor could function as a DR. EphA4 has been shown to function as a DR, the apoptotic activity of which is impaired by its ligand ephrinB3 (Furne et al, 2009).…”

Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

“…Receptor cleavage is important for apoptotic function, as mutation of the cleavage site abolishes cell death induction. DCC, neogenin, Ptc, ALK, EphA4 are cleaved once, roughly in the middle of their intracellular domain (Mehlen et al, 1998;Thibert et al, 2003;Matsunaga et al, 2004;Mourali et al, 2006;Furne et al, 2009). The cleavage site of UNC5 receptors is very close to the plasma membrane (Llambi et al, 2001), whereas RET, Trkc and MET have two cleavage sites A new paradigm in cell signaling and cancer therapy D Goldschneider and P Mehlen (Bordeaux et al, 2000;Foveau et al, 2007;TauszigDelamasure et al, 2007).…”

Section: Drs Are Caspase Substratesmentioning

confidence: 99%

“…In the case of neogenin, the ligand antiapoptotic effect was reported only for chick RGM/ RGMa (Matsunaga et al, 2004) but not for other members of the RGM family or for netrin-1/3/4. EphA4-associated cell death induction is hindered by ephrinB3, but not by its other known ligands, ephrinA1 and ephrinA4 (Furne et al, 2009). With regard to ALK, only ligand-mimicking antibodies have been used because the identity of the receptor's physiological ligand is still a matter of debate.…”

Section: Role Of Ligand Bindingmentioning

confidence: 99%

“…These receptors are named 'dependence receptors.' To date, the dependence receptor (DR) family is composed of more than a dozen members including DCC (deleted in colorectal carcinoma) (Mehlen et al, 1998), UNC5Hs (uncoordinated 5 homologs), neogenin (Matsunaga et al, 2004), p75 NTR (p75 neurotrophin receptor) (Rabizadeh et al, 1993), RET (rearranged during transfection) (Bordeaux et al, 2000), TrkC (tyrosine kinase receptor C) (Tauszig-Delamasure et al, 2007), Ptc (patched) (Thibert et al, 2003), EphA4 (ephrin type A receptor 4) (Furne et al, 2009), ALK (anaplastic lymphoma kinase) (Mourali et al, 2006), MET (Tulasne et al, 2004) and some integrins (Stupack et al, 2001). All of them are involved in both nervous system development and cancer progression.…”

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confidence: 99%

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Dependence receptors: a new paradigm in cell signaling and cancer therapy

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Section: Role Of Ligand Bindingmentioning

confidence: 93%

Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

Section: Drs Are Caspase Substratesmentioning

confidence: 99%

Section: Role Of Ligand Bindingmentioning

confidence: 99%

mentioning

confidence: 99%

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Dependence receptors: a new paradigm in cell signaling and cancer therapy

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Irreversible modifications of receptor tyrosine kinases

2018

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Each group of the 56 receptor tyrosine kinases (RTK) binds with one or more soluble growth factors and coordinates a vast array of cellular functions. These outcomes are tightly regulated by inducible post-translational events, such as tyrosine phosphorylation, ubiquitination, ectodomain shedding, and regulated intramembrane proteolysis. Because of the delicate balance required for appropriate RTK function, cells may become pathogenic upon dysregulation of RTKs themselves or their post-translational covalent modifications. For example, reduced ectodomain shedding and decreased ubiquitination of the cytoplasmic region, both of which enhance growth factor signals, characterize malignant cells. Whereas receptor phosphorylation and ubiquitination are reversible, proteolytic cleavage events are irreversible, and either modification might alter the subcellular localization of RTKs. Herein, we focus on ectodomain shedding by metalloproteinases (including ADAM family proteases), cleavage within the membrane or cytoplasmic regions of RTKs (by gamma-secretases and caspases, respectively), and complete receptor proteolysis in lysosomes and proteasomes. Roles of irreversible modifications in RTK signaling, pathogenesis, and pharmacology are highlighted.

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Glial cells in adult neurogenesis

Morrens

Broeck

Kempermann

2011

Glia

163

101

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Adult neurogenesis is an exceptional feature of the adult brain and in an intriguing way bridges between neuronal and glial neurobiology. Essentially, all classes of glial cells are directly or indirectly linked to this process. Cells with astrocytic features, for example, serve as radial glia-like stem cells in the two neurogenic regions of the adult brain, the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles, producing new neurons, create a microenvironment permissive for neurogenesis, and are themselves generated alongside the new neurons in an associated but independently regulated process. Oligodendrocytes are generated from precursor cells intermingled with those generating neurons in an independent lineage. NG2 cells have certain precursor cell properties and are found throughout the brain parenchyma. They respond to extrinsic stimuli and injury but do not generate neurons even though they can express some preneuronal markers. Microglia have positive and negative regulatory effects as constituents of the "neurogenic niche". Ependymal cells play incompletely understood roles in adult neurogenesis, but under certain conditions might exert (back-up) precursor cell functions. Glial contributions to adult neurogenesis can be direct or indirect and are mediated by mechanisms ranging from gap-junctional to paracrine and endocrine. As the two neurogenic regions differ between each other and both from the non-neurogenic rest of the brain, the question arises in how far regionalization of both the glia-like precursor cells as well as of the glial cells determines site-specific "neurogenic permissiveness." In any case, however, "neurogenesis" appears to be an essentially glial achievement.

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EphrinB3 is an anti-apoptotic ligand that inhibits the dependence receptor functions of EphA4 receptors during adult neurogenesis

Cited by 85 publications

References 35 publications

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Irreversible modifications of receptor tyrosine kinases

Glial cells in adult neurogenesis

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