A Notch updated

Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 04/2009; 184(5):621-9. DOI: 10.1083/jcb.200811141
Source: PubMed

ABSTRACT Cell-cell signaling mediated by the Notch receptor is iteratively involved in numerous developmental contexts, and its dysregulation has been associated with inherited genetic disorders and cancers. The core components of the signaling pathway have been identified for some time, but the study of the modulation of the pathway in different cellular contexts has revealed many layers of regulation. These include complex sugar modifications in the extracellular domain as well as transit of Notch through defined cellular compartments, including specific endosomes.

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Available from: An-Chi Tien, Jun 10, 2015
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    • "Cleavage at the S2 site by ADAMs activates the receptor, which is still anchored to the plasma membrane . The γ-secretase enzyme complex (Presenilin 1 and 2, Nicastrin, APH1 and PEN2) cleaves the NOTCH receptor at S3 and S4 sites and subsequently releases the active NOTCH- ICD (De Strooper et al. 1999; Tien et al. 2009). The two nuclear localization signals on the NOTCH-ICD direct its translocation to the nucleus. "
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    ABSTRACT: The NOTCH pathway is an evolutionarily conserved signalling network, which is fundamental in regulating developmental processes in invertebrates and vertebrates (Gazave et al. in BMC Evol Biol 9:249, 2009). It regulates self-renewal (Butler et al. in Cell Stem Cell 6:251-264, 2010), differentiation (Auderset et al. in Curr Top Microbiol Immunol 360:115-134, 2012), proliferation (VanDussen et al. in Development 139:488-497, 2012) and apoptosis (Cao et al. in APMIS 120:441-450, 2012) of diverse cell types at various stages of their development. NOTCH signalling governs cell-cell interactions and the outcome of such responses is highly context specific. This makes it impossible to generalize about NOTCH functions as it stimulates survival and differentiation of certain cell types, whereas inhibiting these processes in others (Meier-Stiegen et al. in PLoS One 5:e11481, 2010). NOTCH was first identified in 1914 in Drosophila and was named after the indentations (notches) present in the wings of the mutant flies (Bigas et al. in Int J Dev Biol 54:1175-1188, 2010). Homologs of NOTCH in vertebrates were initially identified in Xenopus (Coffman et al. in Science 249:1438-1441, 1990) and in humans NOTCH was first identified in T-Acute Lymphoblastic Leukaemia (T-ALL) (Ellisen et al. in Cell 66:649-61, 1991). NOTCH signalling is integral in neurogenesis (Mead and Yutzey in Dev Dyn 241:376-389, 2012), myogenesis (Schuster-Gossler et al. in Proc Natl Acad Sci U S A 104:537-542, 2007), haematopoiesis (Bigas et al. in Int J Dev Biol 54:1175-1188, 2010), oogenesis (Xu and Gridley in Genet Res Int 2012:648207, 2012), differentiation of intestinal cells (Okamoto et al. in Am J Physiol Gastrointest Liver Physiol 296:G23-35, 2009) and pancreatic cells (Apelqvist et al. in Nature 400:877-881, 1999). The current review will focus on NOTCH signalling in normal and malignant blood cell production or haematopoiesis.
    Journal of Cell Communication and Signaling 02/2015; 9(1). DOI:10.1007/s12079-015-0271-0
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    • "Almost at the same time the newly identified PS homologue in Caenorhabditis elegans, sel-12, was reported to be involved in the Notch signaling pathway (Levitan and Greenwald 1995). This highly conserved pathway is essential for metazoan development (Del Amo et al. 1992; Tien et al. 2009; Sethi and Kang 2011). PS has been implicated in the cleavage of the Notch receptor. "
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    ABSTRACT: Presenilin is a central, catalytic component of the γ-secretase complex which conducts intramembrane cleavage of various protein substrates. Although identified and mainly studied through its role in the development of amyloid plaques in Alzheimer disease, γ-secretase has many other important functions. The complex seems to be evolutionary conserved throughout the Metazoa, but recent findings in plants and Dictyostelium discoideum as well as in archeons suggest that its evolution and functions might be much more diversified than previously expected. In this review, a selective survey of the multitude of functions of presenilins and the γ-secretase complex is presented. Following a brief overview of γ-secretase structure, assembly and maturation, three functional aspects are analyzed: (1) the role of γ-secretase in autophagy and phagocytosis; (2) involvement of the complex in signaling related to endocytosis; and (3) control of calcium fluxes by presenilins.
    Protoplasma 03/2013; 250(5). DOI:10.1007/s00709-013-0494-y · 3.17 Impact Factor
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    • "Notch signaling is further regulated by activation on the early endosomes in the receiving cells (Tien et al., 2009). Several of the positive signaling regulators/facilitators identified in recent years, including Deltex, Syx7/Avl, Rabenosyn-5, and Vps45, are trafficking components that may bring Notch to the endosomes (Hori et al., 2004; Lu and Bilder, 2005; Morrison et al., 2008). "
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    ABSTRACT: Intracellular trafficking underlies cellular functions ranging from membrane remodeling to receptor activation. During multicellular organ development, these basic cell biological functions are required as both passive machinery and active signaling regulators. Exocytosis, endocytosis, and recycling of several key signaling receptors have long been known to actively regulate morphogenesis and pattern formation during Drosophila eye development. Hence, intracellular membrane trafficking not only sets the cell biological stage for receptor-mediated signaling but also actively controls signaling through spatiotemporally regulated receptor localization. In contrast to eye development, the role of intracellular trafficking for the establishment of the eye-to-brain connectivity map has only recently received more attention. It is still poorly understood how guidance receptors are spatiotemporally regulated to serve as meaningful synapse formation signals. Yet, the Drosophila visual system provides some of the most striking examples for the regulatory role of intracellular trafficking during multicellular organ development. In this review we will first highlight the experimental and conceptual advances that motivate the study of intracellular trafficking during Drosophila visual system development. We will then illuminate the development of the eye, the eye-to-brain connectivity map and the optic lobe from the perspective of cell biological dynamics. Finally, we provide a conceptual framework that seeks to explain how the interplay of simple genetically encoded intracellular trafficking events governs the seemingly complex cellular behaviors, which in turn determine the developmental product.
    Developmental Neurobiology 12/2011; 71(12):1227-45. DOI:10.1002/dneu.20940 · 4.19 Impact Factor
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