NB-3/Notch1 Pathway via Deltex1 Promotes Neural Progenitor Cell Differentiation into Oligodendrocytes

Cui, Xiaoying; Hu, Qidong; Tekaya, M.; Shimoda, Yasushi; Ang, Beng-Ti; Nie, Duyu; Lee, Sun; Hu, Wei-Ping; Karsak, Meliha; Duka, Tanya; Takeda, Yasuo; Ou, Lian-Yun; Dawe, Gavin S.; Yu, F.; Ahmed, Sohail; Jin, Lianhong; Schachner, Melitta; Watanabe, Kazutada; Arsenijévic, Yvan; Xiao, Zhicheng

doi:10.1074/jbc.m313505200

Cited by 128 publications

(124 citation statements)

References 33 publications

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…Delta1, Jagged1) and noncanonical ligands (DNER (39), F3/contactin (40), NB3 (41), and Nov/ CCN3 (42), we have been unable to induce Notch activity on a reporter construct when MAGP-2 is added in trans, either through conditioned medium or co-culture with MAGP-2-expressing fibroblasts. 4 The observation that MAGPs interact with Notch only where expressed in the same cell may reflect a relevant mechanism to restrict MAGP activation of Notch to a subset of cells, a potentially important limit given the pleiotropic effects of Notch signaling in a wide variety of cells.…”

Section: Discussionmentioning

confidence: 99%

Microfibrillar Proteins MAGP-1 and MAGP-2 Induce Notch1 Extracellular Domain Dissociation and Receptor Activation

Miyamoto

Lau

Hein

et al. 2006

Journal of Biological Chemistry

113

123

View full text Add to dashboard Cite

Unlike most receptors, Notch serves as both the receiver and direct transducer of signaling events. Activation can be mediated by one of five membrane-bound ligands of either the Delta-like (-1, -2, -4) or Jagged/Serrate (-1, -2) families. Alternatively, dissociation of the Notch heterodimer with consequent activation can also be mediated experimentally by calcium chelators or by mutations that destabilize the Notch1 heterodimer, such as in the human disease T cell acute lymphoblastic leukemia. Here we show that MAGP-2, a protein present on microfibrils, can also interact with the EGF-like repeats of Notch1. Co-expression of MAGP-2 with Notch1 leads to both cell surface release of the Notch1 extracellular domain and subsequent activation of Notch signaling. Moreover, we demonstrate that the C-terminal domain of MAGP-2 is required for binding and activation of Notch1. Based on the high level of homology, we predicted and further showed that MAGP-1 can also bind to Notch1, cause the release of the extracellular domain, and activate signaling. Notch1 extracellular domain release induced by MAGP-2 is dependent on formation of the Notch1 heterodimer by a furinlike cleavage, but does not require the subsequent ADAM metalloprotease cleavage necessary for production of the Notch signaling fragment. Together these results demonstrate for the first time that the microfibrillar proteins MAGP-1 and MAGP-2 can function outside of their role in elastic fibers to activate a cellular signaling pathway.Notch signaling is best known for its role in cell fate determination and is critical for regulating multiple cellular processes in many different tissues, including those of the nervous, hematopoietic, and vascular systems (1). Controlled by membrane-tethered ligands on apposing cells, ligand binding initiates canonical Notch signaling and leads to the proteolytic release of the Notch intracellular domain (NICD).2 The NICD fragment travels to the nucleus, interacts with a DNA-binding protein CSL (CBF1/Su(H)/LAG-1), and activates expression of target genes such as HES1.At least three proteolytic events are required for Notch activation through CSL. The first cleavage is ligand-independent and occurs during maturation of the co-linear Notch protein. Either during trafficking or at the cell surface, Notch is cleaved by a furin-like convertase into two fragments, the extracellular domain (N EC ) and the transmembrane-anchored intracellular domain (N TM ), that remain associated through non-covalent interactions (2-4). This "heterodimer" is the predominant form of Notch on the plasma membrane and is required for ligand-induced CSL-dependent Notch signaling (4). Accordingly, ligand engagement by the heterodimeric Notch receptor leads to sequential ADAM and ␥-secretase cleavage events that facilitate the release of NICD from its membrane tether to activate signaling (5, 6).Underscoring the importance of Notch signaling is the finding that more than 50% of T-ALL patient samples tested so far carry activating mutations of Notch1 (N1) ...

show abstract

Section: Discussionmentioning

confidence: 99%

Microfibrillar Proteins MAGP-1 and MAGP-2 Induce Notch1 Extracellular Domain Dissociation and Receptor Activation

Miyamoto

Lau

Hein

et al. 2006

Journal of Biological Chemistry

113

123

View full text Add to dashboard Cite

show abstract

“…Upon binding to canonical Delta, Serrate/ Jagged, and Lag-2 ligands, Notch activation maintains the pool of NPCs in their undifferentiated state and allows for the generation of OPCs (Artavanis-Tsakonas et al 1999), thus blocking OL maturation through these ligands (Wang et al 1998). In addition, NB-3 and F3/contactin, two neural cell adhesion molecules, act as non-canonical Notch ligands participating in OL generation (Cui et al 2004;Hu et al 2003). NB-3 triggers NICD nuclear translocation, promoting oligodendrogenesis from progenitor cells and OPC maturation via Deltex1 (Cui et al 2004).…”

Section: Underlying Mechanisms In Demyelination/ Remyelination Processesmentioning

confidence: 99%

“…In addition, NB-3 and F3/contactin, two neural cell adhesion molecules, act as non-canonical Notch ligands participating in OL generation (Cui et al 2004;Hu et al 2003). NB-3 triggers NICD nuclear translocation, promoting oligodendrogenesis from progenitor cells and OPC maturation via Deltex1 (Cui et al 2004). We found that the treatment of demyelinated rats with a single apotransferrin (aTf) (350 ng) injection at the time of CPZ withdrawal induces a marked increase in myelin deposition as compared to the spontaneous remyelination observed in control animals (Adamo et al 2006).…”

Section: Underlying Mechanisms In Demyelination/ Remyelination Processesmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

View full text Add to dashboard Cite

Demyelination is a pathological process characterized by the loss of myelin around axons. In the central nervous system, oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Remyelination is a regenerative process by which myelin sheaths are restored to demyelinated axons, resolving functional deficits. This process is often deficient in demyelinating diseases such as multiple sclerosis (MS), and the reasons for the failure of repair mechanisms remain unclear. The characterization of these mechanisms and the factors involved in the proliferation, recruitment, and differentiation of oligodendroglial progenitor cells is key in designing strategies to improve remyelination in demyelinating disorders. First, a very dynamic combination of different molecules such as growth factors, cytokines, chemokines, and different signaling pathways is tightly regulated during the remyelination process. Second, factors unrelated to this pathology, i.e., age and genetic background, may impact disease progression either positively or negatively, and in particular, age-related remyelination failure has been proven to involve oligodendroglial cells aging and their intrinsic capacities among other factors. Third, nutrients may either help or hinder disease progression. Experimental evidence supports the anti-inflammatory role of omega-6 and omega-3 polyunsaturated fatty acids through the competitive inhibition of arachidonic acid, whose metabolites participate in inflammation, and the reduction in T cell proliferation. In turn, vitamin D intake and synthesis have been associated with lower MS incidence levels, while vitamin D-gene interactions might be involved in the pathogenesis of MS. Finally, dietary polyphenols have been reported to mitigate demyelination by modulating the immune response.

show abstract

“…1, middle). On the other hand, binding of atypical Notch ligands to Notch receptor in the absence of typical Notch ligands gives rise to the association of CSL, NICD and Deltex (11)(12)(13). Because Deltex affects the DNA-binding preferentiality of CSL, the CSL-NICD-Deltex complex activates the transcription of unique target genes, such as MAG (Fig.…”

mentioning

confidence: 99%

“…DNER is a type I transmembrane protein with extracellular EGF-like repeats (11). F3/Contactin and NB-3 are glycosyl phosphatidylinositol (GPI)-anchored proteins with immunoglobulin-like domains and EGF-like repeats (12,13). DLL1, DLL3, DLL4, JAG1 and JAG2 with DSL domain are typical Notch ligands with higher affinity, while DNER, F3/Contactin and NB-3 without DSL domain are atypical Notch ligands with lower affinity.…”

mentioning

confidence: 99%